Tumor necrosis factor-a augments lipopolysaccharide-induced suppressor of cytokine signalling 3 (SOCS-3) protein expression by preventing the degradation

• Published in: Immunology Vol. 129; no. 1; pp. 97 - 104
• Main Authors: Dagvadorj, Jargalsaikhan, Naiki, Yoshikazu, Tumurkhuu, Gantsetseg, Noman, Abu Shadat Mohammod, Iftakhar-E-Khuda, Imtiaz, Komatsu, Takayuki, Koide, Naoki, Yoshida, Tomoaki, Takashi Yokochi
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2010
• Subjects: Animals; Cells, Cultured; Cysteine Proteinase Inhibitors - pharmacology; Cytokines; Leupeptins - pharmacology; Lipopolysaccharides - pharmacology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - pathology; Male; Mice; Mice, Knockout; Phosphorylation; Protein Stability - drug effects; Protein Tyrosine Phosphatases - metabolism; Proteins; Recombinant Proteins - pharmacology; Rodents; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - biosynthesis; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - immunology; TNF inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2009.03154.x

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.