SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model

Wei-Dong Zhou, Zhou WD, Zhou Wu, Hui-Ming Yang, Yang HM, Huimin Yang, Wang Q, Qin Wang, Dong-Yin Su, Dongxue Su, Su DY, Liu FA, Fu-An Liu, Fuan Liu, Min Zhao, Zhao M, Qing Chen, Chen QH, Qiong-Hua Chen, Qing-Xi Chen, Chen QX
Human Reproduction · 2010 · vol. 25(12) , pp. 3110–3116 · doi:10.1093/humrep/deq287 · PMID:20956267 · W2108045411
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SB203580, a p38 MAPK inhibitor, reduced endometriotic lesion size in mice by down-regulating proinflammatory cytokines and proteolytic factors.

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Abstract

BACKGROUND: p38 mitogen-activated protein kinase (p38 MAPK), a regulator of inflammation, may play a role in the pathogenesis of endometriosis (EM). We studied the effect of SB203580, a p38 MAPK inhibitor, on the development of EM in a mouse model. METHODS: EM was induced in BALB/c mice by peritoneal injection of endometrium-rich fragments. Mice (n = 15) were injected i.p. for 24 days with SB203580 and 15 mice served as positive controls (EM group). Sham-operated mice received carrier only. Peritoneal fluid (PF) cells were collected for protein/mRNA analysis. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins were measured using enzyme-linked immunosorbent assay and mRNAs by RT-PCR. Phosphorylation of p38 MAPK was evaluated by western blotting. RESULTS: SB203580 decreased the weight and size (P < 0.05 versus EM) of endometriotic lesions in BALB/c mice. IL-1β, TNF-α, MMP-2 and MMP-9 mRNA levels were decreased in peritoneal cells of the SB203580 versus EM group (P < 0.01, P < 0.05, P < 0.05 and P < 0.05, respectively). Concentrations of IL-1β, TNF-α, MMP-2 and MMP-9 proteins in PF were reduced in the SB203580 versus EM group (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). Compared with the sham-operated group, phosphorylation of p38 MAPK in the EM group was increased, and this was down-regulated by SB203580 (P < 0.01). CONCLUSIONS: SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM.

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Condition tags

endometriosis

MeSH descriptors

Cytokines Endometriosis Imidazoles Pyridines Animals Cytokines Down-Regulation Endometriosis Female Imidazoles Interleukin-1beta Interleukin-1beta Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Matrix Metalloproteinase 9 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases

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