Tumor necrosis factor-a augments lipopolysaccharide-induced  suppressor of cytokine signalling 3 (SOCS-3) protein expression  by preventing the degradation.
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.
Dagvadorj
Jargalsaikhan
J
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
Naiki
Yoshikazu
Y
Tumurkhuu
Gantsetseg
G
Noman
Abu Shadat Mohammod
AS
Iftakhar-E-Khuda
Imtiaz
I
Komatsu
Takayuki
T
Koide
Naoki
N
Yoshida
Tomoaki
T
Takashi Yokochi
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*
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