Thrombin induces IL-10 production in microglia as a negative feedback regulator of TNF-alpha release.
Interleukin-10 (IL-10), an immunosuppressive cytokine, is produced by monocyte/macrophage lineage cells, T cells, and B cells in the immune system. Here, we show that thrombin induces IL-10 expression in cultured rat microglia. Thrombin treatment increases IL-10 mRNA expression after 3 h and IL-10 release into the culture medium 12 h after thrombin treatment. Neutralizing antibodies against IL-10 significantly enhanced TNF-alpha release from thrombin-treated microglia. IL-10 release was suppressed by an inhibitor of p38 MAPK, SB203580 but not by an inhibitor of ERK pathway, PD98059, whereas both SB203580 and PD98059 inhibited TNF-alpha release. These results suggest that thrombin induces IL-10 and TNF-alpha expression through different signaling mechanisms, and that IL-10 inhibits TNF-alpha release as a negative feedback regulation.
Kim
Kyung You
KY
Brain Disease Research Center, Ajou University School of Medicine, Ajou University, San-5 Wonchon-dong, Paldal-gu, Suwon, Kyunggi-do, Korea 442-749.
Kim
Min Young
MY
Choi
Hee Seung
HS
Jin
Byung Kwan
BK
Kim
Seung Up
SU
Lee
Yong Beom
YB
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001930:Brain Injuries / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005246:Feedback / Q000187:drug effects / Q000502:physiology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D000906:Antibodies; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin