title: Bacterial endotoxin induces IL-20 expression in the glial cells.
abstract: The regulatory mechanisms leading to IL-20 expression during infection have not been elucidated. In the present study, we found that bacterial lipopolysaccharide (LPS) induced IL-20 expression in the primary cultured glial cells and RAW264.7 macrophage cell line. Pretreatment with protein synthesis inhibitor puromycin or cycloheximide failed to inhibit the expression of IL-20, suggesting that the expression was not dependent on de novo protein synthesis. Myeloid differentiation factor 88 (MyD88) is an important adaptor molecule for Toll-like receptor signaling. We observed complete inhibition of LPS-induced expression of IL-20 in the primary cultured glial cells prepared from MyD88-deficient mice. Furthermore, a p38 MAP kinase inhibitor, SB203580, inhibited LPS-induced expression of IL-20 mRNA. LPS-induced p38 MAP kinase phosphorylation was delayed in MyD88-deficient glial cells. Therefore, it is suggested that LPS induces IL-20 expression through MyD88-p38-dependent mechanisms. As dexamethasone inhibited LPS-induced IL-20 expression, the expression of IL-20 is regulated by a negative feedback loop mediated through glucocorticoids. Therefore, it is suggested that IL-20 may play a crucial role in inflammatory conditions in the brain.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-Ku, Sapporo 060-0812, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hosoi
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Wada
authors.forename: Sawako
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000172:deficiency / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D007093:Imidazoles; D007378:Interleukins; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011691:Puromycin; D003907:Dexamethasone; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C422042:interleukin 20