The role of transforming growth factor beta-1 in the progression of HIV/AIDS and development of Non-AIDS-defining fibrotic disorders

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Abstract

© 2017 Theron, Anderson, Rossouw and Steel. Even after attainment of sustained viral suppression following implementation of highly active antiretroviral therapy, HIV-infected persons continue to experience persistent, low-grade, systemic inflammation. Among other mechanisms, this appears to result from ongoing microbial translocation from a damaged gastrointestinal tract. This HIV-related chronic inflammatory response is paralleled by counteracting, but only partially effective, biological anti-inflammatory processes. Paradoxically, however, this anti-inflammatory response not only exacerbates immunosuppression but also predisposes for development of non-AIDS-related, non-communicable disorders. With respect to the pathogenesis of both sustained immunosuppression and the increased frequency of non-AIDS-related disorders, the anti-inflammatory/profibrotic cytokine, transforming growth factor-β1 (TGF-β1), which remains persistently elevated in both untreated and virally suppressed HIV-infected persons, may provide a common link. In this context, the current review is focused on two different, albeit related, harmful activities of TGF-β1 in HIV infection. First, on the spectrum of anti-inflammatory/immunosuppressive activities of TGF-β1 and the involvement of this cytokine, derived predominantly from T regulatory cells, in driving disease progression in HIV-infected persons via both non-fibrotic and profibrotic mechanisms. Second, the possible involvement of sustained elevations in circulating and tissue TGF-β1 in the pathogenesis of non-AIDS-defining cardiovascular, hepatic, pulmonary and renal disorders, together with a brief comment on potential TGF-β1-targeted therapeutic strategies.

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APA

Theron, A. J., Anderson, R., Rossouw, T. M., & Steel, H. C. (2017, November 2). The role of transforming growth factor beta-1 in the progression of HIV/AIDS and development of Non-AIDS-defining fibrotic disorders. Frontiers in Immunology. Frontiers Media S.A. https://doi.org/10.3389/fimmu.2017.01461

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