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: Toru Hosoi, Sachiyo Wada, Sawako Suzuki, Yasunobu Okuma, Shizuo Akira, Tadashi Matsuda, Yasuyuki Nomura
• Journal: Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 130 Issue 1-2 Pg. 23-9 (Nov 04 2004) ISSN: 0169-328X [Print] Netherlands
• PMID: 15519673 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens, Differentiation
• Enzyme Inhibitors
• Glucocorticoids
• Imidazoles
• Interleukins
• Lipopolysaccharides
• Myd88 protein, mouse
• Myeloid Differentiation Factor 88
• Protein Synthesis Inhibitors
• Pyridines
• RNA, Messenger
• Receptors, Immunologic
• Puromycin
• Dexamethasone
• Cycloheximide
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• p38 Mitogen-Activated Protein Kinases
• SB 203580
• interleukin 20

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Animals, Newborn
• Antigens, Differentiation (physiology)
• Blotting, Western (methods)
• Brain (cytology)
• Cells, Cultured
• Cycloheximide (pharmacology)
• Dexamethasone (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation (drug effects)
• Glucocorticoids (pharmacology)
• Imidazoles (pharmacology)
• Interleukins (genetics, metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88
• Neuroglia (drug effects, metabolism)
• Nitric Oxide Synthase (metabolism)
• Nitric Oxide Synthase Type II
• Protein Synthesis Inhibitors (pharmacology)
• Puromycin (pharmacology)
• Pyridines (pharmacology)
• RNA, Messenger (biosynthesis)
• Receptors, Immunologic (deficiency, physiology)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• p38 Mitogen-Activated Protein Kinases (metabolism)