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IN SITU DETECTION OF SOCS AND CYTOKINE EXPRESSION IN THE UTERINE CERVIX FROM HIV/HPV COINFECTED WOMEN
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Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Serviços de Imunologia. Rio de Janeiro, RJ, Brasil.
University Hospitals. Department of Pathology. Columbus, OH, USA.
University Hospitals. Department of Pathology. Columbus, OH, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Departamento de Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Departamento de Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Laboratório Multidisciplinar. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Serviços de Imunologia. Rio de Janeiro, RJ, Brasil.
David Geffen School of Medicine. Departments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Serviços de Imunologia. Rio de Janeiro, RJ, Brasil.
University Hospitals. Department of Pathology. Columbus, OH, USA.
University Hospitals. Department of Pathology. Columbus, OH, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Departamento de Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Departamento de Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Laboratório Multidisciplinar. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Serviços de Imunologia. Rio de Janeiro, RJ, Brasil.
David Geffen School of Medicine. Departments of Obstetrics and Gynecology and Microbiology, Immunology and Molecular Genetics. Los Angeles, CA, USA.
Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Serviços de Imunologia. Rio de Janeiro, RJ, Brasil.
Abstract
The purpose of this study was to look for associations between a newly described class of suppressors of cytokine signaling (SSI/SOCS) andcytokine expression in the uterine cervix from HIV/HPV coinfected women. We examined the pro-inflammatory cytokines TNF-α and IL-6 since their expressions are linked and responsible for many aspects of both localized and systemic inflammatory responses. Further, expression of SSI/SOCS has been implicated in the negative feedback regulation of cytokine receptor signaling. PCR-amplified HIV-1 cDNA was noted mainly in the stroma, showing a perivascular distribution, and most of the infected cells colabeled with the macrophage marker CD68. The distribution of IL-6 and TNF-α was in the same area to HIV-1 and much greater than normal cervices from women with no evidence of viral infection. SOCS/SSI-1 and -3 mRNA positive cells in the uterine cervix were commonly detected in these noninfected cervical tissues; however, very few cells that contained SOCS were evident in areas where HIV-1, TNF-α, and IL-6 expressing cells were found. This suggests that viral-related suppression of SOCS/SSI-1-3 expression may be a factor in the marked local enhancement of TNF-α and IL-6 production which, in turn, may help facilitate viral spread; however, further studies should be done in order to elucidate the exact mechanisms of SOCS in the cervix.
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