title: The anti-inflammatory activity of curcumin protects the genital mucosal epithelial barrier from disruption and blocks replication of HIV-1 and HSV-2.
abstract: Inflammation is a known mechanism that facilitates HIV acquisition and the spread of infection. In this study, we evaluated whether curcumin, a potent and safe anti-inflammatory compound, could be used to abrogate inflammatory processes that facilitate HIV-1 acquisition in the female genital tract (FGT) and contribute to HIV amplification. Primary, human genital epithelial cells (GECs) were pretreated with curcumin and exposed to HIV-1 or HIV glycoprotein 120 (gp120), both of which have been shown to disrupt epithelial tight junction proteins, including ZO-1 and occludin. Pre-treatment with curcumin prevented disruption of the mucosal barrier by maintaining ZO-1 and occludin expression and maintained trans-epithelial electric resistance across the genital epithelium. Curcumin pre-treatment also abrogated the gp120-mediated upregulation of the proinflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6, which mediate barrier disruption, as well as the chemokines IL-8, RANTES and interferon gamma-induced protein-10 (IP-10), which are capable of recruiting HIV target cells to the FGT. GECs treated with curcumin and exposed to the sexually transmitted co-infecting microbes HSV-1, HSV-2 and Neisseria gonorrhoeae were unable to elicit innate inflammatory responses that indirectly induced activation of the HIV promoter and curcumin blocked Toll-like receptor (TLR)-mediated induction of HIV replication in chronically infected T-cells. Finally, curcumin treatment resulted in significantly decreased HIV-1 and HSV-2 replication in chronically infected T-cells and primary GECs, respectively. All together, our results suggest that the use of anti-inflammatory compounds such as curcumin may offer a viable alternative for the prevention and/or control of HIV replication in the FGT.
authors: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors: Victor H
authors: VH
authors: Ferreira
authors: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors: Aisha
authors: A
authors: Nazli
authors: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors: Sara E
authors: SE
authors: Dizzell
authors: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors: Kristen
authors: K
authors: Mueller
authors: Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors: Charu
authors: C
authors: Kaushic
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018925:Chemokines / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects; D006558:Herpes Genitalis / Q000188:drug therapy*; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D019169:Jurkat Cells; D018613:Microscopy, Confocal; D009092:Mucous Membrane / Q000187:drug effects*; D062793:Occludin / Q000378:metabolism; D060737:Reproductive Tract Infections / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D015850:Interleukin-6; D062793:Occludin; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D003474:Curcumin