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Tumor necrosis factor‐α augments lipopolysaccharide‐induced suppressor of cytokine signalling 3 (SOCS‐3) protein expression by preventing the degradation
Author(s) -
Dagvadorj Jargalsaikhan,
Naiki Yoshikazu,
Tumurkhuu Gantsetseg,
Shadat Mohammod Noman Abu,
IftakharEKhuda Imtiaz,
Komatsu Takayuki,
Koide Naoki,
Yoshida Tomoaki,
Yokochi Takashi
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03154.x
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , phosphorylation , cytokine , protein tyrosine phosphatase , suppressor of cytokine signalling , biology , tyrosine phosphorylation , cancer research , microbiology and biotechnology , endocrinology , socs3 , immunology , stat3
Summary The regulatory role of tumour necrosis factor‐α (TNF‐α) on the expression of suppressor of cytokine signalling 3 (SOCS‐3) in response to lipopolysaccharide (LPS) was examined using peritoneal macrophages from TNF‐α‐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‐α‐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‐α‐deficient mice. The addition of exogenous TNF‐α augmented the LPS‐induced SOCS‐3 expression in macrophages from TNF‐α‐deficient mice. The pulse chase analysis suggested augmented degradation of LPS‐induced SOCS‐3 protein in macrophages from TNF‐α‐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‐α‐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‐α prevented the degradation of SOCS‐3 protein via inhibition of the tyrosine phosphorylation in LPS‐stimulated macrophages.