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  

Oleh:

Wei-Dong, Zhou ; Yang, Hui-Ming ; Qin, Wang ; Su, Dong-Yin ; Liu, Fu-An ; Zhao, Min ; Qiong-Hua, Chen ; Qing-Xi, Chen

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Human Reproduction vol. 25 no. 12 (Dec. 2010), page 3101-3109 .
Topik: REPRODUCTIVE BIOLOGY; endometriosis; mouse model; p38 mitogen-activated protein kinase; cytokines; proteolytic factors
Fulltext: Human Reproduction, Vol.25, No.12 pp. 3110–3116, 2010.pdf (176.41KB)

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Perpustakaan FK Nomor Panggil: H07.K.2010.04 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

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)-1ß, tumor necrosis factor (TNF)-a, 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-1ß, TNF-a, 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-1ß, TNF-a, 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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