title: ER stress-mediated regulation of immune function under glucose-deprived condition in glial cells: up- and down-regulation of PGE2 + IFNγ-induced IL-6 and iNOS expressions.
abstract: Glucose metabolism plays central role in maintaining brain function. Under ischemic condition, where glucose levels were reduced, glial cells induce pro-inflammatory cytokine production. In the present study, we found prostaglandin (PG) E2+interferon (IFN) γ-induced interleukin (IL)-6 production was enhanced under glucose-deprived condition in the primary cultured glial cells. On the other hand, to our surprise, we found that PGE2+IFNγ-induced iNOS expression was attenuated under glucose-deprived condition. These dual effects would be mediated through endoplasmic reticulum (ER) stress, because we observed (1) up-regulation of GRP78 and CHOP under glucose-deprived condition, which was inhibited by chemical chaperon TMAO, and (2) treatment with TMAO inhibited IL-6 production under glucose-deprived condition. By activating theses responses glial cells may protect neurons because we observed increased neuronal cell viability in the immune-activated glial cell conditioned medium. Overall, our results suggest a link between ER stress and immune reactions under glucose-deprived condition in the glial cells.
authors.affiliation: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oba
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D045744:Cell Line, Tumor; D015232:Dinoprostone / Q000276:immunology* / Q000494:pharmacology; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000276:immunology*; D005947:Glucose / Q000172:deficiency*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D051742:Transcription Factor CHOP / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D051742:Transcription Factor CHOP; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D005947:Glucose; D015232:Dinoprostone
keywords: Endoplasmic reticulum stress; Glial cells; Glucose; Inducible nitric oxide synthase; Interleukin-6