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Endocannabinoids alleviate proinflammatory conditions by modulating innate immune response in muller glia during inflammation
Author(s) -
Krishnan Gopinath,
Chatterjee Nivedita
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22380
Subject(s) - endocannabinoid system , proinflammatory cytokine , biology , muller glia , innate immune system , mapk/erk pathway , inflammation , immune system , cytokine , neuroprotection , microbiology and biotechnology , protein kinase a , cannabinoid , immunology , neuroscience , kinase , receptor , biochemistry , stem cell , progenitor cell
Abstract Muller cells play a prominent role in inflammatory conditions of the retina. They are part of the retinal innate immune response. The endocannabinoid system functions as an immune modulator in both the peripheral immune system as well as the central nervous system. We hypothesized that the neuroprotective ability of exogenous endocannabinoids in the retina is partially mediated through Muller glia. This study reports that exposure to endocannabinoids in activated but not resting primary human Muller glia inhibit production of several proinflammatory cytokines, while elevating anti‐inflammatory mediators. Cytokine generation in activated Muller glia is regulated by endocannabinoids through the mitogen‐activated protein kinase (MAPK) family at multiple signaling stages. Anandamide (AEA) acts to control MAPK phosphorylation through MKP‐1. Both AEA and 2‐arachidonoylglycerol (2‐AG) inhibit the transcription factor NF‐κB and increases the regulatory protein, IL1‐R‐associated kinase 1‐binding protein 1. Endocannabinoids also increase expression of Tristetraprolin in activated Muller cells, which is implicated in affecting AU‐rich proinflammatory cytokine mRNA. We demonstrate that exogenous application of AEA and 2‐AG aid in retinal cell survival under inflammatory conditions by creating an anti‐inflammatory milieu. Endocannabinoids or synthetic cannabinoid therapy may therefore orchestrate a molecular switch to bias the innate immune system suchthat the balance of pro‐ and anti‐inflammatory cytokine generation creates a prosurvival milieu. © 2012 Wiley Periodicals, Inc.