Canna~Fangled Abstracts

Endocannabinoids affect innate immunity of Muller glia during HIV-1 Tat cytotoxicity.

By January 10, 2014No Comments
2014 Jan 10. pii: S1044-7431(14)00002-5. doi: 10.1016/j.mcn.2014.01.001. [Epub ahead of print]

pm8Endocannabinoids 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.
Copyright © 2014. Published by Elsevier Inc.

KEYWORDS:

(2-AG), (AEA), (AM-251), (AM-630), (CB1), (CB2), (FR180204), (IRAK1BP1), (Ly294002), (MKP-1), (MKP-2), (Ro-318220), (SB203580), (SP600125), (TTP), (U0126), 1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene), 2(MAP-2), 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-onehydrochloride), 2-arachidonoylglycerol, 3-[3-[2,5-Dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]propyl carbamimidothioic acid ester mesylate), 4-[5-(4-Fluorophenyl)-2-[4 (methylsulfonyl)phenyl]-1H-imidazol-4-yl]pyridine), 5-(2-Phenyl-pyrazolo[1,5-a]pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridazin-3-ylamine), 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone), Anthra[1-9-cd]pyrazol-6(2H)-one), Cannabinoid receptor type 1, Cannabinoid receptor type 2, HIV1 Tat, IL-1R-associated kinase 1 binding protein 1, Microtubule-associated protein, Mitogen-activated protein kinase phosphatase-1, Muller glia, N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide, N-arachidonoylethanolamide, Tristetraprolin, endocannabinoids, mitogen-activated protein kinase phosphatase-2, retina

PMID:

 24418364
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