SHP-2/NF-?B pathway mediates the antagonism of lipoxin A4 on EL-1?-induced production of IL-6 in glomerular mesangial cells
- VernacularTitle:蛋白酪氨酸磷酸酶2/核因子-?B途径介导脂氧素A4拮抗系膜细胞白介素6的合成
- Author:
Shenghua WU
;
Chao LU
;
Ling DONG
;
Xinyou JIANG
- Publication Type:Journal Article
- Keywords:
Lipoxins;
Interleukin;
Nuclear factor-kappa B;
Protein-tyrosine phosphatase;
Mesangial cells
- From:
Chinese Journal of Nephrology
2005;0(07):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine whether lipoxin A4(LXA4) has an antagonistic effect on interleukin (IL)-1?-induced synthesis of IL-6 in glomerular mesangial cells, and to explore its mechanism. Methods Cultured glomerular mesangial cells (GMCs) of rat were treated with IL-1?, with or without preincubation with LXA4. Protein secretion of IL-6 in supernatants was examined analyzed by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 mRNA was determined by RT-PCR. The expression of Src homology 2 (SH2) containing protein-tyrosine phosphatase 2 (SHP-2) was assessed by immunoblotting. Activities of DNA-binding of nuclear factor-kappa B (NF-?B) were measured by electrophoretic mobility shift assay (EMSA). Results The secretion of protein and expression of mRNA of IL-6 in GMCs stimulated by IL-1? were inhibited by LXA4 in a dose-dependent manner. LXA4 reduced the phosphorylation of SHP-2 and activities of NF-?B. Pretreatmnet of GMCs with NF-?B inhibitor pyrrolidine dithio-carbamate (PDTC) blocked both the secretion of IL-6 protein and activation of NF-?B induced by IL-13- Conclusion LXA4 antagonists IL-1?-induced synthesis of IL-6 in GMCs through the pathway of SHP-2/NF-?B signal transduction.
