Chlamydia trachomatis e Inmunidad

Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by Type 2 immunity.

Vicetti Miguel RD¹, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

 

Abstract

Chlamydia trachomatis is an obligate intracellular bacterium sexually transmitted to more than 90 million individuals each year. As this level of infectivity implies, C. trachomatis is a successful human parasite; a success facilitated by its ability to cause asymptomatic infection. Host defense against C. trachomatis in the female genital tract is not well defined, but current dogma suggests infection is controlled largely by T(H)1 immunity. Conversely, it is well established that T(H)2 immunity controls allergens, helminths, and other extracellular pathogens that cause repetitive or persistent T cell stimulation but do not induce the exuberant inflammation that drives T(H)1 and T(H)17 immunity. As C. trachomatis persists in female genital tract epithelial cells but does not elicit over tissue inflammation, we now posit that defense is maintained by Type 2 immune responses that control bacterial growth but minimize immunopathological damage to vital reproductive tract anatomy. Evaluation of this hypothesis may uncover novel mechanisms by which Type 2 immunity can control growth of C. trachomatis and other intracellular pathogens, while confirmation that T(H)2 immunity was selected by evolution to control C. trachomatis infection in the female genital tract will transform current research, now focused on developing vaccines that elicit strong, and therefore potentially tissue destructive, Chlamydia-specific T(H)1 immunity.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Med Hypotheses. 2012 Dec;79(6):713-6. doi: 10.1016/j.mehy.2012.07.032. Epub 2012 Sep 15.

http://www.sciencedirect.com/science/article/pii/S0306987712003568

Md. Rodolfo Vicetti. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Brefeldin A, but not monensin, enables flow cytometric detection of interleukin-4 within peripheral T cells responding to ex vivo stimulation with Chlamydia trachomatis.

Vicetti Miguel RD¹, Maryak SA, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. rdv4@pitt.edu

 

Abstract

Intracellular cytokine staining (ICS) assay optimization should include selection of suitable cytokine secretion inhibitors. Here, peripheral blood mononuclear cells (PBMC) from women with proven history of C. trachomatis genital tract infection were used to compare the ability of brefeldin A (BFA) and monensin (MN) to concurrently trap interferon-γ (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-4, and IL-17 within T cells responding to ex vivo stimulation with chlamydial antigen. While flow cytometric analyses showed similar intracellular levels of TNF, IFN-γ, and IL-17 among T cells treated with BFA or both BFA and MN, markedly more IL-4 was found inside T cells treated with BFA compared to those that received MN or BFA and MN. The latter findings oppose current ICS recommendations informing that ICS results are unaffected by concomitant use of BFA and MN, and also suggests that MN may be an unsuitable cytokine secretion inhibitor for ICS assays designed to measure intracellular IL-4 accumulation.

Copyright © 2012 Elsevier B.V. All rights reserved.

J Immunol Methods. 2012 Oct 31;384(1-2):191-5. doi: 10.1016/j.jim.2012.07.018. Epub 2012 Jul 29.

http://www.sciencedirect.com/science/article/pii/S0022175912002293

Md. Rodolfo Vicetti. Ex-miembro del GII.

Célula Dendríticas y Medroxyprogesterona

Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone acetate prior to mucosal herpes simplex virus type 1 infection.

Vicetti Miguel RD¹, Hendricks RL, Aguirre AJ, Melan MA, Harvey SA, Terry-Allison T, St Leger AJ, Thomson AW, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

Epidemiological studies indicate that the exogenous sex steroid medroxyprogesterone acetate (MPA) can impair cell-mediated immunity, but mechanisms responsible for this observation are not well defined. In this study, MPA administered to mice 1 wk prior to HSV type 1 (HSV-1) infection of their corneal mucosa impaired initial expansion of viral-specific effector and memory precursor T cells and reduced the number of viral-specific memory T cells found in latently infected mice. MPA treatment also dampened expression of the costimulatory molecules CD40, CD70, and CD80 by dendritic cells (DC) in lymph nodes draining acute infection, whereas coculture of such DC with T cells from uninfected mice dramatically impaired ex vivo T cell proliferation compared with the use of DC from mice that did not receive MPA prior to HSV-1 infection. In addition, T cell expansion was comparable to that seen in untreated controls if MPA-treated mice were administered recombinant soluble CD154 (CD40L) concomitant with their mucosal infection. In contrast, the immunomodulatory effects of MPA were infection site dependent, because MPA-treated mice exhibited normal expansion of virus-specific T cells when infection was systemic rather than mucosal. Taken together, our results reveal that the administration of MPA prior to viral infection of mucosal tissue impairs DC activation, virus-specific T cell expansion, and development of virus-specific immunological memory.

J Immunol. 2012 Oct 1;189(7):3449-61. Epub 2012 Aug 31.

http://www.jimmunol.org/content/189/7/3449.long


Md. Rodolfo Vicetti. Ex-miembro del GII.

Dermatología e Inmunología

Mastocitos y basófilos y sus nuevas funciones en inmunología

 Julio E Valdivia-Silva 

1Chemokines Biology Research Laboratory, Instituto de Investigaciones Biomédicas, UNAM, México D.F., México.

ABSTRACT 

Mast cells and basophils have demonstrated to have both beneficial and detrimental functions for the immune system. Additionally to their classic role in pro-inflammatory responses to allergens, they are also involved directly in immunity against different pathogens. Because there are few animals models developed to investigate these cells in vivo, their functions during health and disease remain poorly understood. This review gives a short glance in the development and functional status of mast cells and basophils focusing on immunology concepts necessary to get a major understanding of the mechanisms of disease in different pathological states. 

DERMATOL PERU 2012; VOL 23

http://sisbib.unmsm.edu.pe/bvrevistas/dermatologia/v23_n2/pdf/a04v23n2.pdf

Md PhD Julio Valdivia Silva. Fundador del GII

 

 

HSV-2 y Vaginosis Bacterial

Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women.

Stoner KA¹, Reighard SD, Vicetti Miguel RD, Landsittel D, Cosentino LA, Kant JA, Cherpes TL.

¹Departments of Obstetrics and Gynecology and Reproductive Sciences Pediatrics Medicine Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

 

Abstract

AIM:

The multifactorial etiology of bacterial vaginosis (BV) impedes development of effective treatment and prevention strategies. Herein, we evaluated the effects of herpes simplex virus type 2 (HSV-2), a suspected BV risk factor, on vaginal flora composition.

MATERIALS AND METHODS:

  Correlations between HSV-2 infection and BV were prospectively explored among 12 HSV-2-seropositive women with asymptomatic BV who were asked to collect daily vaginal swab specimens for Gram stain analysis of vaginal flora and determination of HSV-2 shedding frequencies during the 1month before and after metronidazole therapy.

RESULTS:

Unlike prior longitudinal studies that reported rapid fluctuations in vaginal flora composition and frequent episodes of spontaneously resolving BV, we found that 99.4% (310/312) of vaginal smears collected before initiation of metronidazole were consistent with a diagnosis of BV. Effectiveness of metronidazole therapy was also much lower than previously reported in studies not restricting enrollment to HSV-2-seropositive women; we observed a BV recurrence rate of 89% in the first month after completion of therapy while the median time to this recurrence occurred only 14days after treatment.

CONCLUSIONS:

Our study demonstrates BV recalcitrance among HSV-2-infected women and provides additional evidence for a linkage between this chronic viral infection and abnormal vaginal flora. Additional work will be needed to define mechanisms responsible for this correlation and to determine if vaginal flora health of HSV-2-infected women is improved by medications that suppress HSV-2 shedding.

© 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

J Obstet Gynaecol Res. 2012 Jan;38(1):77-83. doi: 10.1111/j.1447-0756.2011.01697.x. Epub 2011 Dec 5.

http://onlinelibrary.wiley.com/doi/10.1111/j.1447-0756.2011.01697.x/abstract;jsessionid=54A78C4B43F9813B882574F362F23AC8.f04t03

Md. Rodolfo Vicetti. Ex-miembro del GII.

Microbiología y RT-PCR

Determination of low bacterial concentrations in hyperarid Atacama soils: comparison of biochemical and microscopy methods with real-time quantitative PCR.

Fletcher LE1, Conley CA, Valdivia-Silva JE, Perez-Montaño S, Condori-Apaza R, Kovacs GT, Glavin DP, McKay CP.

¹Atmospheric, Oceanic, and Planetary Physics, Clarendon Laboratory, University of Oxford, UK. Lauren@atm.ox.ac.uk

 

Abstract

Hyperarid Atacama soils are reported to contain significantly reduced numbers of microbes per gram of soil relative to soils from other environments. Molecular methods have been used to evaluate microbial populations in hyperarid Atacama soils; however, conflicting results across the various studies, possibly caused by this low number of microorganisms and consequent biomass, suggest that knowledge of expected DNA concentrations in these soils becomes important to interpreting data from any method regarding microbial concentrations and diversity. In this paper we compare the number of bacteria per gram of Atacama Desert soils determined by real-time quantitative polymerase chain reaction with the number of bacteria estimated by the standard methods of phospholipids fatty acid analysis, adenine composition (determined by liquid chromatography - time-of-flight mass spectrometry), and SYBR-green microscopy. The number determined by real-time quantitative polymerase chain reaction as implemented in this study was several orders of magnitude lower than that determined by the other three methods and probably underestimates the concentrations of soil bacteria, most likely because of soil binding during the DNA extraction methods. However, the other methods very possibly overestimate the bacteria concentrations owing to desiccated, intact organisms, which would stain positive in microscopy and preserve both adenine and phospholipid fatty acid for the other methods.

Can J Microbiol. 2011 Nov;57(11):953-63. doi: 10.1139/w11-091.

http://www.nrcresearchpress.com/doi/abs/10.1139/w11-091?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#.VbJdMkWdMnU

Md PhD Julio Valdivia Silva. Fundador del GII

Enfermedad Inflamatoria Pélvica

Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research.

Vicetti Miguel RD¹, Chivukula M, Krishnamurti U, Amortegui AJ, Kant JA, Sweet RL, Wiesenfeld HC, Phillips JM, Cherpes TL.

¹University of Pittsburgh School of Medicine, Department of Pediatrics, PA 15224, USA.

 

Abstract

While endometrial neutrophils and plasma cells are criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease (PID) research, plasma cell misidentification and nonspecificity may limit the accuracy of these criteria. Herein, we examined: (1) the identification of endometrial plasma cells with conventional methyl green pyronin-based methodology versus plasma cell-specific (CD138) immunostaining, (2) the prevalence of endometrial plasma cells among women at low risk for PID, and (3) endometrial leukocyte subpopulations among women diagnosed with acute or chronic histologic endometritis by conventional criteria. We observed an absence of CD138+ cells in 25% of endometrial biopsies in which plasma cells had been identified by conventional methodology, while additional immunohistochemical analyses revealed indistinguishable inflammatory infiltrates among women diagnosed with acute or chronic endometritis by conventional criteria. Among women considered at lower risk for PID development, flow cytometric analyses detected plasma cells in 30% of endometrial biopsy specimens, suggesting that these cells, even when accurately identified, only nonspecifically identify upper genital tract inflammatory processes. Combined, our findings underscore the limitations of the criteria used to diagnose histologic endometritis in PID-related research and suggest that satisfactory understanding of PID pathogenesis, treatment, and prevention is hindered by continued use of these criteria.

Copyright © 2011 Elsevier GmbH. All rights reserved.

Pathol Res Pract. 2011 Nov 15;207(11):680-5. doi: 10.1016/j.prp.2011.08.007. Epub 2011 Oct 13.

http://www.sciencedirect.com/science/article/pii/S0344033811002044

Md. Rodolfo Vicetti. Ex-miembro del GII.

Chlamydia trachomatis e Inmunidad

Chlamydia trachomatis infection control programs: lessons learned and implications for vaccine development.

Chavez JM¹, Vicetti Miguel RD, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Rangos Research Center, Room 9123, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.

 

Abstract

Chlamydia trachomatis control efforts that enhance detection and treatment of infected women may paradoxically increase susceptibility of the population to infection. Conversely, these surveillance programs lower incidences of adverse sequelae elicited by genital tract infection (e.g., pelvic inflammatory disease and ectopic pregnancy), suggesting enhanced identification and eradication of C. trachomatis simultaneously reduces pathogen-induced upper genital tract damage and abrogates formation of protective immune responses. In this paper, we detail findings from C. trachomatis infection control programs that increase our understanding of chlamydial immunoepidemiology and discuss their implications for prophylactic vaccine design.

Infect Dis Obstet Gynecol. 2011;2011:754060. doi: 10.1155/2011/754060. Epub 2011 Nov 14.

http://www.hindawi.com/journals/idog/2011/754060/

Md. Rodolfo Vicetti. Ex-miembro del GII.

Infecciones del Tracto Genital

Endometrial leukocyte subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis genital tract infection.

Reighard SD¹, Sweet RL, Vicetti Miguel C, Vicetti Miguel RD, Chivukula M, Krishnamurti U, Cherpes TL.

¹Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.

 

Abstract

OBJECTIVE:

The objective of the study was to characterize endometrial inflammation associated with common genital tract pathogens.

STUDY DESIGN:

The design of the study was the immunohistochemical characterization of the endometrial leukocyte subpopulations from 37 controls and 45 women infected with Chlamydia trachomatis, Neisseria gonorrhoeae, or Trichomonas vaginalis.

RESULTS:

Compared with uninfected women, endocervical infection with C trachomatis, N gonorrhoeae, or T vaginalis was associated with significant increases in endometrial T cells, B cells, plasma cells, and polymorphonuclear leukocytes. Even more substantial increases in T cell, B cell, and plasma cell numbers were detected among women infected endocervically and endometrially with C trachomatis.

CONCLUSION:

Because lower genital tract C trachomatis, N gonorrhoeae, or T vaginalis infections were associated with comparable increases in the same endometrial leukocyte subpopulations, our results suggest the underappreciated involvement of T vaginalis in upper genital tract inflammatory processes. The more robust inflammatory infiltrate associated with C trachomatis endometrial ascension may offer insight into host inflammatory responses associated with pelvic inflammatory disease development.

Copyright © 2011 Mosby, Inc. All rights reserved.

Am J Obstet Gynecol. 2011 Oct;205(4):324.e1-7. doi: 10.1016/j.ajog.2011.05.031. Epub 2011 May 20.

http://www.sciencedirect.com/science/article/pii/S0002937811006594

Md. Rodolfo Vicetti. Ex-miembro del GII.

Dieta y Sindrome Premenstrual

Dietary B vitamin intake and incident premenstrual syndrome.

Chocano-Bedoya PO¹, Manson JE, Hankinson SE, Willett WC, Johnson SR, Chasan-Taber L, Ronnenberg AG, Bigelow C, Bertone-Johnson ER.

¹Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003-9304, USA.

 

Abstract

BACKGROUND:

Thiamine, riboflavin, niacin, vitamin B-6, folate, and vitamin B-12 are required to synthesize neurotransmitters that are potentially involved in the pathophysiology of premenstrual syndrome (PMS).

OBJECTIVE:

The objective was to evaluate whether B vitamin intake from food sources and supplements is associated with the initial development of PMS.

DESIGN:

We conducted a case-control study nested within the Nurses' Health Study II cohort. Participants were free of PMS at baseline (1991). After 10 y of follow up, 1057 women were confirmed as cases and 1968 were confirmed as controls. Dietary information was collected in 1991, 1995, and 1999 by using food-frequency questionnaires.

RESULTS:

Intakes of thiamine and riboflavin from food sources were each inversely associated with incident PMS. For example, women in the highest quintile of riboflavin intake 2-4 y before the diagnosis year had a 35% lower risk of developing PMS than did those in the lowest quintile (relative risk: 0.65; 95% CI: 0.45, 0.92; P for trend = 0.02). No significant associations between incident PMS and dietary intakes of niacin, vitamin B-6, folate, and vitamin B-12 were observed. Intake of B vitamins from supplements was not associated with a lower risk of PMS.

CONCLUSIONS:

We observed a significantly lower risk of PMS in women with high intakes of thiamine and riboflavin from food sources only. Further research is needed to evaluate the effects of B vitamins in the development of premenstrual syndrome.

Am J Clin Nutr. 2011 May;93(5):1080-6. doi: 10.3945/ajcn.110.009530. Epub 2011 Feb 23.

http://ajcn.nutrition.org/content/93/5/1080.long

Md. PhD. Patricia Chocano. Ex miembro del GII.  

Cancer e inmunidad

A caveat for T cell transfer studies: generation of cytotoxic anti-Thy1.2 antibodies in Thy1.1 congenic mice given Thy1.2+ tumors or T cells.

McKenna KC¹, Vicetti Miguel RD, Beatty KM, Bilonick RA.

¹University of Pittsburgh, Eye and Ear Institute, Pittsburgh, PA 15213, USA. mckennakc@upmc.edu

 

Abstract

Thy1.1 congenic B6.PL mice were used to simultaneously monitor Thy1.2+ E.G7-OVA tumors transplanted in the a.c. of the eye and i.v.-transferred tumor-specific Thy1.2+ CTLs to determine mechanisms that inhibit the tumoricidal activity of CTL responses in mice with established ocular tumors. Transferred CTLs were systemically deleted in mice with established ocular tumors. However, this deletion was not a unique mechanism of immune evasion by ocular tumors. Rather, development of Thy1.2+ tumors in the eye or skin of B6.PL mice generated cytotoxic anti-Thy1.2 antibodies that eliminated a subsequent Thy1.2+ T cell transfer. Anti-Thy1.2 immune responses in B6.PL mice were influenced by the route of antigen administration, as the serum concentration of cytotoxic anti-Thy1.2 antibodies was 92-fold greater in mice with eye tumors in comparison with mice with skin tumors. In addition, anti-Thy1.2 immune responses were detected in B6.PL mice given naïve Thy1.2+ T cells i.p. but not i.v. Anti-Thy1.2 responses were augmented in B6.PL mice with ocular Thy1.2+ EL-4 tumors that did not express OVA, suggesting immunodominance of OVA antigen over Thy1.2. Thy1.1+ T cells given i.p. was not immunogenic in Thy1.2 congenic mice. These data reaffirm that the introduction of antigens in the a.c. induces robust antibody responses. Experimentation using allotypic differences in Thy1 between donor cells and recipient mice must consider cytotoxic anti-Thy1 antibody generation in the interpretation of results.

J Leukoc Biol. 2011 Feb;89(2):291-300. doi: 10.1189/jlb.0610333. Epub 2010 Oct 19.

http://www.jleukbio.org/content/89/2/291.long

Md. Rodolfo Vicetti. Ex-miembro del GII.

Cancer e Inmunidad

CTL induction of tumoricidal nitric oxide production by intratumoral macrophages is critical for tumor elimination.

Vicetti Miguel RD¹, Cherpes TL, Watson LJ, McKenna KC.

¹Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

 

Abstract

To characterize mechanisms of CTL inhibition within an ocular tumor microenvironment, tumor-specific CTLs were transferred into mice with tumors developing within the anterior chamber of the eye or skin. Ocular tumors were resistant to CTL transfer therapy whereas skin tumors were sensitive. CTLs infiltrated ocular tumors at higher CTL/tumor ratios than in skin tumors and demonstrated comparable ex vivo effector function to CTLs within skin tumors indicating that ocular tumor progression was not due to decreased CTL accumulation or inhibited CTL function within the eye. CD11b(+)Gr-1(+)F4/80(-) cells predominated within ocular tumors, whereas skin tumors were primarily infiltrated by CD11b(+)Gr-1(-)F4/80(+) macrophages (Ms), suggesting that myeloid derived suppressor cells may contribute to ocular tumor growth. However, CD11b(+) myeloid cells isolated from either tumor site suppressed CTL activity in vitro via NO production. Paradoxically, the regression of skin tumors by CTL transfer therapy required NO production by intratumoral Ms indicating that NO-producing intratumoral myeloid cells did not suppress the effector phase of CTL. Upon CTL transfer, tumoricidal concentrations of NO were only produced by skin tumor-associated Ms though ocular tumor-associated Ms demonstrated comparable expression of inducible NO synthase protein suggesting that NO synthase enzymatic activity was compromised within the eye. Correspondingly, in vitro-activated Ms limited tumor growth when co-injected with tumor cells in the skin but not in the eye. In conclusion, the decreased capacity of Ms to produce NO within the ocular microenvironment limits CTL tumoricidal activity allowing ocular tumors to progress.

J Immunol. 2010 Dec 1;185(11):6706-18. doi: 10.4049/jimmunol.0903411. Epub 2010 Nov 1.

 http://www.jimmunol.org/content/185/11/6706.long

Md. Rodolfo Vicetti. Ex-miembro del GII.

Dieta y Sindrome Premenstrual

Dietary vitamin D intake, 25-hydroxyvitamin D3 levels and premenstrual syndrome in a college-aged population.

Bertone-Johnson ER¹, Chocano-Bedoya PO, Zagarins SE, Micka AE, Ronnenberg AG.

¹Division of Biostatistics and Epidemiology, Department of Public Health, University of Massachusetts, Amherst, MA 01003-9304, USA. ebertone@schoolph.umass.edu

 

Abstract

High dietary intake of vitamin D may reduce the risk of premenstrual syndrome (PMS), perhaps by affecting calcium levels, cyclic sex steroid hormone fluctuations, and/or neurotransmitter function. Only a small number of previous studies have evaluated this relationship and none have focused on young women. We assessed this relationship in a cross-sectional analysis within the UMass Vitamin D Status Study. Between 2006 and 2008, 186 women aged 18-30 (mean age=21.6 years) completed a validated food frequency questionnaire, additional questionnaires to assess menstrual symptoms and other health and lifestyle factors, and provided a fasting blood sample collected during the late luteal phase of their menstrual cycle. Among all study participants, results suggested the possibility of an inverse association between intake of vitamin D from food sources and overall menstrual symptom severity, though were not statistically significant; mean intakes in women reporting menstrual symptom severity of none/minimal, mild, and moderate/severe were 253, 214, and 194 IU/day, respectively (P=0.18). From among all study participants, 44 women meeting standard criteria for PMS and 46 women meeting control criteria were included in additional case-control analyses. In these women, after adjustment for age, body mass index, smoking status and total calcium intake, higher intake of vitamin D from foods was associated with a significant lower prevalence of PMS. Women reporting vitamin D intake from food sources of >or=100 IU/day had a prevalence odds ratio of 0.31 compared to those reporting<100 IU/day (95% confidence interval=0.10-0.98). Late luteal phase 25-hydroxyvitamin D3 levels were not associated with prevalent PMS. Results from this pilot study suggest that a relationship between vitamin D and PMS is possible, though larger studies are needed to further evaluate this relationship and to investigate whether 25-hydroxyvitamin D3 levels in the follicular or early luteal phases of the menstrual cycle may be related to PMS risk.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

J Steroid Biochem Mol Biol. 2010 Jul;121(1-2):434-7. doi: 10.1016/j.jsbmb.2010.03.076. Epub 2010 Apr 14.

http://www.sciencedirect.com/science/article/pii/S0960076010001755

Md. PhD. Patricia Chocano. Ex miembro del GII.   

Cancer y Citocinas

Actin cytoskeleton participation in the onset of IL-1beta induction of an invasive mesenchymal-like phenotype in epithelial MCF-7 cells.

 

Franco-Barraza J1, Valdivia-Silva JE, Zamudio-Meza H, Castillo A, García-Zepeda EA, Benítez-Bribiesca L, Meza I.

¹Departamento de Biomedicina Molecular, CINVESTAV-IPN, Apartado, México, D.F., México.

Abstract

BACKGROUND:

Interleukin 1 beta (IL-1beta) and other inflammatory cytokines are reported to induce phenotypic changes in epithelial breast cancer tumor cells related to increased invasiveness. Mechanisms involved in the process are not well understood.

METHODS:

The noninvasive breast cancer epithelial cell line MCF-7 was used to investigate the IL-1beta-induced phenotype. Live cells expressing EGFP-actin were monitored for cell morphology changes and actin cytoskeleton dynamics by time-lapse video microscopy in the presence of IL-1beta and specific inhibitors of actin signaling pathways. Chemotaxis, invasion of Matrigel, MMP activity and expression of S100A4 in cells treated with IL-1beta were assessed by migration assays, zymograms and immunoblots.

RESULTS:

Exposure to IL-1beta specifically induced a change in MCF-7 cells from a typical epithelial morphology into elongated cells, showing numerous dynamic actin-rich lamellae and peripheral ruffles characteristic of fibroblasts. These cells could scatter from compact cell colonies and respond to chemoattractants such as the homing-associated chemokine CXCL-12. Pharmacological blockage of actin signaling pathways and negative mutants of RhoGTPases revealed that actin reorganization and enhanced motility are regulated via PI3K/Rac 1 activation. IL-1beta-stimulated cells expressed the metastasis promoter S100A4, increased secretion of active MMP-9 and MMP-2 and invasion of extracellular matrix proteins.

CONCLUSIONS:

IL-1beta induces a PI3K/Rac 1-regulated reorganization of the actin cytoskeleton of MCF-7 cells that is required for cell scattering, elongation and migration. The enhanced motility is accompanied by expression of protein markers correlated with invasive behavior.
Copyright 2010 IMSS. Published by Elsevier Inc. All rights reserved.

Arch Med Res. 2010 Apr;41(3):170-81. doi: 10.1016/j.arcmed.2010.04.010.

http://www.sciencedirect.com/science/article/pii/S0188440910001013

Md PhD Julio Valdivia Silva. Fundador del GII

Influenza

Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1) virus in influenza-like illness patients in Peru.

 

Laguna-Torres VA1, Gómez J, Aguilar PV, Ampuero JS, Munayco C, Ocaña V, Pérez J, Gamero ME, Arrasco JC, Paz I, Chávez E, Cruz R, Chavez J, Mendocilla S, Gomez E, Antigoni J, Gonzalez S, Tejada C, Chowell G, Kochel TJ; Peru Influenza working group.

 ¹Virology Department, United States Naval Medical Research Center Detachment, Lima, Perú. alberto.laguna@med.navy.mil

 

Abstract

BACKGROUND:

We describe the temporal variation in viral agents detected in influenza like illness (ILI) patients before and after the appearance of the ongoing pandemic influenza A (H1N1) (pH1N1) in Peru between 4-January and 13-July 2009.

METHODS:

At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW) 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD) in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR).

RESULTS:

We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW) 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5%) from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima) followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle) cities during our study period. The city of Iquitos (Jungle) had the highest number of influenza B cases and only one pH1N1 case.

CONCLUSIONS:

The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

PLoS One. 2010 Jul 27;5(7):e11719. doi: 10.1371/journal.pone.0011719.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0011719

Md. Irmia Paz. Tutora del GII

Ojé y Coagulación sanguínea

 Efecto in vitro del látex de Ficus insipida sobre la cascada de la coagulación sanguínea.

Fernando Concha-Benavente ¹

1Médico Cirujano miembro del Grupo de Investigación en Inmunología y Academia Peruana de Medicina Molecular. Facultad de Medicina de la Universidad Nacional de San Agustín. Arequipa, Perú.

SUMMARY
We need to search for new natural drugs yielding pharmacological active principles to be used as an alternative to conventional therapies. For this reason, we proposed to study Ficus insipida, an amazonian plant that its latex has been used for years as an Antihelmintic agent but its anticoagulant effect has been only superficially studied. Objective: To corroborate the in vitro anticoagulant effect and to determine upon which of the coagulation pathways acts the latex of Ficus insipida. Material and methods: The latex of Ficus insipida was obtained and prepared at different concentrations. Then, samples of peripheral blood from 5 donors were taken using sodium citrate to avoid blood clotting; the samples were mixed with the latex dilutions and centrifuged, after that, the plasma was extracted to form a plasma pool from each latex concentration. Finally, the Prothrombin Time (PT) and the Partial Thromboplastin Time (PTT) were determined, respectively. Results: The results obtained demonstrated that the latex of Ficus insipida delays the PT at concentrations equal or higher than 0.03125% (V/V), and both the PT and PTT at concentrations equal or higher than 0.15% (V/V). Conclusions: This data allow us to affirm that the latex of Ficus insipida has a dose-dependent in vitro anticoagulant effect upon the extrinsic coagulation pathway at concentrations equal or higher than

0.03125% (V/V). Additionally, at concentrations equal or higher than 0.15% (V/V) it has a potent anticoagulant effect over both coagulation pathways.(Rev Med Hered 2010;21:146-152).

KEY WORDS: Blood coagulation factors, prothrombin time, partial thromboplastin time, ficus, anticoagulant agents.

 

Rev Med Hered v.21 n.3 Lima jul. 2010

http://www.scielo.org.pe/scielo.php?script=sci_arttext&pid=S1018-130X2010000300006

Md.PhD. Fernando Concha-Benavente. Ex-miembro del GII

HSV-1 y Hormonas

17-beta estradiol promotion of herpes simplex virus type 1 reactivation is estrogen receptor dependent.

Vicetti Miguel RD¹, Sheridan BS, Harvey SA, Schreiner RS, Hendricks RL, Cherpes TL.

¹Graduate Program in Immunology, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. [corrected].

 

Abstract

Correlations between estrogen and herpes simplex virus (HSV) reactivation from latency have been suggested by numerous clinical reports, but causal associations are not well delineated. In a murine HSV-1 corneal infection model, we establish 17-beta estradiol (17-betaE) treatment of latently infected ovariectomized mice induces viral reactivation, as demonstrated by increased viral load and increased immediate-early viral gene expression in the latently infected trigeminal ganglia (TG). Interestingly, the increased HSV reactivation occurred in the absence of inhibition of viral specific CD8(+) T-cell effector function. 17-betaE administration increased HSV reactivation in CD45(+) cell-depleted TG explant cultures, providing further support that leukocyte-independent effects on latently infected neurons were responsible for the increased reactivation. The drug-induced increases in HSV copy number were not recapitulated upon in vivo treatment of latently infected estrogen receptor alpha-deficient mice, evidence that HSV reactivation promoted by 17-betaE was estrogen receptor dependent. These findings provide additional framework for the emerging conceptualization of HSV latency as a dynamic process maintained by complex interactions among multiple cooperative and competing host, viral, and environmental forces. Additional research is needed to confirm whether pregnancy or hormonal contraceptives containing 17-betaE also promote HSV reactivation from latency in an estrogen receptor-dependent manner.

J Virol. 2010 Jan;84(1):565-72. doi: 10.1128/JVI.01374-09.

http://jvi.asm.org/content/84/1/565.long

Md. Rodolfo Vicetti. Ex-miembro del GII.

Cancer de mama y Citocinas

Effect of pro-inflammatory cytokine stimulation on human breast cancer: implications of chemokine receptor expression in cancer metastasis.

Valdivia-Silva JE1, Franco-Barraza J, Silva AL, Pont GD, Soldevila G, Meza I, García-Zepeda EA.

Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, Circuito exterior s/n, C.P. 04510 DF, Mexico.

 

Abstract

Interactions between tumour cells and microenvironments may affect their growth and metastasis formation. In search for a better understanding of the role of cellular mediators in the progression of cancer, we investigated the effect of pro-inflammatory cytokines IL-1, IL-6, TNF-alpha and IFN-gamma on the regulation of expression of chemokine receptors CXCR4, CXCR2, CX3CR1, CCR9, and CCR5 in the human breast cancer cell line MCF-7. Our results showed that IL-1 increased CXCR4 expression whereas TNF-alpha increased CX3CR1, CCR9 and CCR5. Interestingly, this regulation was not homogeneous, emphasizing the inherent heterogeneity in cancer that may be responsive to specific inflammatory microenvironments.

Cancer Lett. 2009 Oct 8;283(2):176-85. doi: 10.1016/j.canlet.2009.03.040. Epub 2009 May 5.

http://www.ncbi.nlm.nih.gov/pubmed/19409696 

Md. Julio Valdivia Silva PhD : Fundador del GII

Pre-eclampsia e Inflamación

Expression of Inflammatory Factors and Increasing of the Intima-Media Thickness in Pre-Eclampsia: Evidence of Maternal and Neonatal Arteriosclerotic Risk

Julio E. Valdivia-Silva^{a, b}, Alfredo Cárdenas^a, Sirlei Medina^a

a Grupo de Investigación en Inmunología. División de Biología Vascular. Departamento de Inmunología y Microbiología. Universidad Nacional San Agustín. Arequipa. Perú

b Laboratorio de Investigación en Biología de las Quimiocinas. Instituto de Investigaciones Biomédicas. Universidad Nacional Autónoma de México. México DF. México

ABSTRACT

Introduction

Pre-eclampsia is a pathological condition characterized by vascular damage produced by systemic factors released from the placenta. These factors include oxygen free radicals, growth factors and inflammatory cytokines that are products released by the placenta during hypoxia cycles. Although, there is evidence of endothelial dysfunction during preeclampsia, there is no evidence of structural changes in the maternal peripheral vasculature or expression of pathological factors which could be considered as arteriosclerotic risk.

Methods

We compared the plasma levels of vascular endothelial growth factor and its soluble receptor sVEGFR-1/sFlt-1 between 16 healthy pregnant women and 24 with pre-eclampsia at term, using the ELISA test. We correlated the expression of hypoxia-inducible factors and the CD40L by RT -PCR and Western blot of endothelial cells of the maternal brachial artery, and measured the Intima-Media- Thickness (IMT) and Flow- Mediated Vasodilation (FMD) by peripheral vascular ultrasound. A P value < 0.05 was considered as statistically significant.

Results

The pre-eclamptic women had high levels of plasma sVEGFR-1/sFlt-1, which directly correlated with the expression of HIF-2α and CD40L in endothelial cells, whereas HIF-1α was significantly diminished. Curiously, the IMT was increased in pregnant women with pre-eclampsia, coinciding with a marked decrease in the FMD.

Conclusions

Our results demonstrate that molecules involved in the pathophysiology of atherosclerosis are increased in the peripheral vasculature, with a significant thickening of the arterial intima of patients with pre-eclampsia, a condition that predisposes to maternal arteriosclerosis and could be extrapolated to a future neonatal risk.

Clínica e Investigación en Arteriosclerosis 09/2009; 21(5). DOI:10.1016/S0214-9168(09)72684-1  

http://www.sciencedirect.com/science/article/pii/S0214916809726841

Md PhD Julio Valdivia Silva. Fundador del GII

Md MSc Alfredo Cárdenas. Past-President del GII

Md Sirlei Medina. Ex miembro del GII

Influenza

Influenza-Like Illness Sentinel Surveillance in Peru

 

Laguna-Torres VA1, Gómez J, Ocaña V, Aguilar P, Saldarriaga T, Chavez E, Perez J, Zamalloa H, Forshey B, Paz I, Gomez E, Ore R, Chauca G, Ortiz E, Villaran M, Vilcarromero S, Rocha C, Chincha O, Jiménez G, Villanueva M, Pozo E, Aspajo J, Kochel T.

¹US Naval Medical Research Center Detachment, Lima, Peru. alberto.laguna@med.navy.mil

Abstract

BACKGROUND:

Acute respiratory illnesses and influenza-like illnesses (ILI) are a significant source of morbidity and mortality worldwide. Despite the public health importance, little is known about the etiology of these acute respiratory illnesses in many regions of South America. In 2006, the Peruvian Ministry of Health (MoH) and the US Naval Medical Research Center Detachment (NMRCD) initiated a collaboration to characterize the viral agents associated with ILI and to describe the clinical and epidemiological presentation of the affected population.

METHODOLOGY/PRINCIPAL FINDINGS:

Patients with ILI (fever > or =38 degrees C and cough or sore throat) were evaluated in clinics and hospitals in 13 Peruvian cities representative of the four main regions of the country. Nasal and oropharyngeal swabs, as well as epidemiological and demographic data, were collected from each patient. During the two years of this study (June 2006 through May 2008), a total of 6,835 patients, with a median age of 13 years, were recruited from 31 clinics and hospitals; 6,308 were enrolled by regular passive surveillance and 527 were enrolled as part of outbreak investigations. At least one respiratory virus was isolated from the specimens of 2,688 (42.6%) patients, with etiologies varying by age and geographical region. Overall the most common viral agents isolated were influenza A virus (25.1%), influenza B virus (9.7%), parainfluenza viruses 1, 2, and 3, (HPIV-1,-2,-3; 3.2%), herpes simplex virus (HSV; 2.6%), and adenoviruses (1.8%). Genetic analyses of influenza virus isolates demonstrated that three lineages of influenza A H1N1, one lineage of influenza A H3N2, and two lineages of influenza B were circulating in Peru during the course of this study.

CONCLUSIONS:

To our knowledge this is the most comprehensive study to date of the etiologic agents associated with ILI in Peru. These results demonstrate that a wide range of respiratory pathogens are circulating in Peru and this fact needs to be considered by clinicians when treating patients reporting with ILI. Furthermore, these data have implications for influenza vaccine design and implementation in South America.

 PLoS One. 2009 Jul 1;4(7):e6118. doi: 10.1371/journal.pone.0006118.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006118

Md. Irmia Paz. Tutora del GII