title: ER stress upregulated PGE₂/IFNγ-induced IL-6 expression and down-regulated iNOS expression in glial cells.
abstract: The disruption of endoplasmic reticulum (ER) function can lead to neurodegenerative disorders, in which inflammation has also been implicated. We investigated the possible correlation between ER stress and immune function using glial cells. We demonstrated that ER stress synergistically enhanced prostaglandin (PG) E₂ + interferon (IFN) γ-induced interleukin (IL)-6 production. This effect was mediated through cAMP. Immune-activated glial cells produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress inhibited PGE₂ + IFNγ-induced iNOS expression. Similar results were obtained when cells were treated with dbcAMP + IFNγ. Thus, cAMP has a dual effect on immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS expression under ER stress. Therefore, our results suggest a link between ER stress and immune reactions in neurodegenerative diseases.
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: Miya
authors.initials: M
authors.lastname: Honda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oba
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000235:genetics; D015232:Dinoprostone / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism*; D009569:Nitric Oxide / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D015850:Interleukin-6; D009569:Nitric Oxide; D007371:Interferon-gamma; D000242:Cyclic AMP; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone