title: Tumor necrosis factor-a augments lipopolysaccharide-induced  suppressor of cytokine signalling 3 (SOCS-3) protein expression  by preventing the degradation.
abstract: The regulatory role of tumour necrosis factor-a (TNF-a) on the expression of suppressor of cytokine signalling 3 (SOCS-3) in response to lipopolysaccharide (LPS) was examined using peritoneal macrophages from TNF-a-deficient mice. The LPS-induced SOCS-3 expression was markedly augmented in macrophages from wild-type mice whereas such augmentation was not seen in the cells from TNF-a-deficient mice. However, there was no significant difference in the level of SOCS-3 messenger RNA expression between macrophages from wild-type mice and those from TNF-a-deficient mice. The addition of exogenous TNF-a augmented the LPS-induced SOCS-3 expression in macrophages from TNF-a-deficient mice. The pulse chase analysis suggested augmented degradation of LPS-induced SOCS-3 protein in macrophages from TNF-a-deficient mice. Moreover, MG 132, a 26S proteasome inhibitor, sustained the LPS-induced SOCS-3 expression in those cells. The tyrosine phosphorylation of SOCS-3 was definitely induced in LPS-stimulated macrophages from TNF-a-deficient mice but not wild-type mice. A tyrosine phosphatase inhibitor enhanced the tyrosine phosphorylation of SOCS-3 in wild-type mice and accelerated the degradation. Therefore, it was suggested that TNF-a prevented the degradation of SOCS-3 protein via inhibition of the tyrosine phosphorylation in LPS-stimulated macrophages.
authors.affiliation: Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Jargalsaikhan
authors.initials: J
authors.lastname: Dagvadorj
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Naiki
authors.forename: Gantsetseg
authors.initials: G
authors.lastname: Tumurkhuu
authors.forename: Abu Shadat Mohammod
authors.initials: AS
authors.lastname: Noman
authors.forename: Imtiaz
authors.initials: I
authors.lastname: Iftakhar-E-Khuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.lastname: Takashi Yokochi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D055550:Protein Stability / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D017027:Protein Tyrosine Phosphatases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde