title: Differential immune mechanism to HIV-1 Tat variants and its regulation by AEA [corrected].
abstract: In the retina, Müller glia is a dominant player of immune response. The HIV-1 transactivator viral protein (Tat) induces production of several neurotoxic cytokines in retinal cells. We show that HIV-1 clades Tat B and C act differentially on Müller glia, which is reflected in apoptosis, activation of cell death pathway components and pro-inflammatory cytokines. The harsher immune-mediated pathology of Tat B, as opposed to milder effects of Tat C, manifests at several signal transduction pathways, notably, MAPK, STAT, SOCS, the NFκB signalosome, and TTP. In activated cells, anandamide (AEA), acting as an immune-modulator, suppresses Tat B effect through MKP-1 but Tat C action via MEK-1. AEA lowers nuclear NF-κB and TAB2 for both variants while elevating IRAK1BP1 in activated Müller glia. Müller glia exposed to Tat shows enhanced PBMC attachment. Tat-induced increase in leukocyte adhesion to Müller cells can be mitigated by AEA, involving both CB receptors. This study identifies multiple signalling components that drive immune-mediated pathology and contribute to disease severity in HIV clades. We show that the protective effects of AEA occur at various stages in cytokine generation and are clade-dependant.
authors.affiliation: 1] L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai, 600006 India [2] Research Scholar, CeNTAB, School of Chemical and Biotechnology, SASTRA University, Tanjore, India.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Krishnan
authors.affiliation: L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai, 600006 India.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000276:immunology* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D063388:Endocannabinoids / Q000276:immunology* / Q000494:pharmacology; D063928:Ependymoglial Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D053284:Polyunsaturated Alkamides / Q000276:immunology* / Q000494:pharmacology; D055815:Young Adult; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000494:pharmacology*
chemical_list: D001095:Arachidonic Acids; D016207:Cytokines; D063388:Endocannabinoids; D007155:Immunologic Factors; D053284:Polyunsaturated Alkamides; D054322:tat Gene Products, Human Immunodeficiency Virus; C078814:anandamide