title: Interleukin (IL)-10 attenuates lipopolysaccharide-induced IL-6 production via inhibition of IkappaB-zeta activity by Bcl-3.
abstract: The inhibitory effect of interleukin-10 (IL-10), an anti-inflammatory cytokine, on lipopolysaccharide (LPS)-induced IL-6 production was characterized by simultaneous stimulation of RAW 264.7 cells with LPS and IL-10. The presence of IL-10 significantly inhibited LPS-induced IL-6 production at a transcriptional level. The expression of IkappaB-zeta, which promotes IL-6 production, was induced in response to LPS and it was definitely suppressed in the presence of IL-10. Further, IL-10 inhibited LPS-induced NF-kappaB activation. A pharmacological inhibitor of NF-kappaB prevented LPS-induced IkappaB-zeta expression, suggesting that IL-10 might inhibit LPS-induced IkappaB-zeta expression via the inactivation of NF-kappaB. In LPS- and IL-10-stimulated cells, the expression of Bcl-3 that inhibits NF-kappaB activation was significantly augmented. Introduction of Bcl-3 siRNA abolished IL-10-mediated IkappaB-zeta inhibition. In the presence of Bcl-3, siRNA IL-10 failed to inhibit LPS-induced IL-6 production. Therefore, it was suggested that Bcl-3 induced by IL-10 might reduce LPS-induced IkappaB-zeta activity via inactivation of NF-kappaB and that reduced IkappaB-zeta activity failed to promote LPS-induced IL-6 production.
authors: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors: Jargalsaikhan
authors: J
authors: Dagvadorj
authors: Yoshikazu
authors: Y
authors: Naiki
authors: Gantsetseg
authors: G
authors: Tumurkhuu
authors: Abu Shadat Mohammod
authors: AS
authors: Noman
authors: Imtiaz
authors: I
authors: Iftekar-E-Khuda
authors: Naoki
authors: N
authors: Koide
authors: Takayuki
authors: T
authors: Komatsu
authors: Tomoaki
authors: T
authors: Yoshida
authors: Takashi
authors: T
authors: Yokochi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D000081242:B-Cell Lymphoma 3 Protein; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C485947:Nfkbiz protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001241:Aspirin