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 = 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.
Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, China.
Wei-Dong
WD
Zhou
Hui-Ming
HM
Yang
Qin
Q
Wang
Dong-Yin
DY
Su
Fu-An
FA
Liu
Min
M
Zhao
Qiong-Hua
QH
Chen
Qing-Xi
QX
Chen
D000818:Animals; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation; D004715:Endometriosis / Q000517:prevention & control*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011725:Pyridines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D016207:Cytokines; D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093642:SB 203580