title: Endocannabinoids affect innate immunity of Muller glia during HIV-1 Tat cytotoxicity.
abstract: In the retina, increased inflammatory response can cause visual impairment during HIV infection in spite of successful anti-retroviral therapy (HAART). The HIV-1 Tat protein is implicated in neurodegeneration by eliciting a cytokine response in cells of the CNS, including glia. The current study investigated whether innate immune response in human retinal Muller glia could be immune-modulated to combat inflammation. Endocannabinoids, N-arachidonoylethanolamide and 2-arachidonoylglycerol are used to alleviate Tat-induced cytotoxicity and rescue retinal cells. The neuroprotective mechanism involved suppression in production of pro-inflammatory and increase of anti-inflammatory cytokines, mainly through the MAPK pathway. The MAPK regulation was primarily by MKP-1. Both endocannabinoids regulated cytokine production by affecting at the transcriptional level the NF-κB complex, including IRAK1BP1 and TAB2. Stability of cytokine mRNA is likely to have been influenced through tristetraprolin. These findings have direct relevance in conditions like immune-recovery uveitis where anti-retroviral therapy has helped immune reconstitution. In such conditions drugs to combat overwhelming inflammatory response would need to supplement HAART. Endocannabinoids and their agonists may be thought of as neurotherapeutic during certain conditions of HIV-1 induced inflammation.
authors.affiliation: L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 41 College Road, Chennai 600006, India; 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. Electronic address: chatterjee.nivedita@gmail.com.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Chatterjee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D063388:Endocannabinoids / Q000494:pharmacology*; D063928:Ependymoglial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051816:Tristetraprolin / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000633:toxicity*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D016207:Cytokines; D063388:Endocannabinoids; D005989:Glycerides; D016328:NF-kappa B; D053284:Polyunsaturated Alkamides; C410585:TAB2 protein, human; D051816:Tristetraprolin; D054322:tat Gene Products, Human Immunodeficiency Virus; C094503:glyceryl 2-arachidonate; C507768:IRAK1 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; C078814:anandamide
keywords: Endocannabinoids; HIV1 Tat; Muller glia; Retina