title: Regulatory effect of SOCS on NF-kappaB activity in murine monocytes/macrophages.
abstract: The suppressor of cytokine signaling (SOCS) group of proteins has been implicated in regulation of various cytokine signaling and in a negative crosstalk between distinct signaling pathways. Interleukin-10 (IL-10) and LPS were known to induce expression of SOCS-3 in neutrophils and monocytes/macrophages. IL-10 was also reported to inhibit a proinflammatory signal-induced NF-kappaB activation in monocytes and peripheral T lymphocytes. The effects of increased SOCS-3 expression upon IL-10 regulation of NF-kappaB activation have not yet been demonstrated. Here we examined the effects of SOCS-3 on NF-kappaB activity. SOCS-3 did not induce any alterations in NF-kappaB activity induced by LPS or TNF-alpha. However, it enhanced RelA-dependent kappaB promoter activity when cotransfected with RelA. Similar results were observed with SOCS-1. In contrast, SOCS-2 did not show any regulatory effects on RelA activity. Analysis of C-terminal truncation mutants of SOCS-1 and SOCS-3 demonstrated that the SOCS box and its N-terminal region, a less well-conserved linker region were important for SOCS-3 activation of RelA. In contrast, the SOCS box itself was critical for SOCS-1 to activate RelA. These results suggest that SOCS proteins can enhance the effects of NF-kappaB/Rel proteins, and therefore, further modulate immune and inflammatory responses.
authors.affiliation: Department of Dermatology, The Catholic Research Institutes of Medical Science, Seoul, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Kyoung-Eun
authors.initials: KE
authors.lastname: Kim
authors.forename: Ha-Young
authors.initials: HY
authors.lastname: Hwang
authors.forename: Tae Yoon
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D010586:Phagocytes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha