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
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 ¼ 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.
... d carrier only. Peritoneal fluid (PF) cells were collected for protein/mRNA analysis. Interleukin (IL)-1b, 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-1b, 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-1b, 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.