FR 167653, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis in a murine model.
In various cells including endometriotic cells, p38 mitogen-activated protein kinase (MAPK) plays essential roles for inflammation, an etiological factor for endometriosis. We evaluated the effect of FR 167653, a p38 MAPK inhibitor, on the development of endometriosis using a murine model. As an endometriosis model, estradiol-treated ovariectomized BALB/c mice were injected intraperitoneally with endometrial fragments of the syngenic donor mice. The animals were injected with either 30mg/kg FR 167653 or only vehicle (control) s.c. twice a day, starting 2 days before endometrial injection. Three weeks later, the peritoneal fluids and the developed endometriotic lesions were collected. Both the weight of all the endometriotic lesions per mouse and the concentrations of interleukin-6 and monocyte chemoattractant protein-1 in the peritoneal fluid were significantly lower in the FR 167653-treated mice than in the control mice. These findings suggest that FR 167653 may inhibit the development of endometriosis possibly by suppressing peritoneal inflammatory status.
Yoshino
Osamu
O
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Osuga
Yutaka
Y
Koga
Kaori
K
Hirota
Yasushi
Y
Hirata
Tetsuya
T
Ruimeng
Xie
X
Na
Li
L
Yano
Tetsu
T
Tsutsumi
Osamu
O
Taketani
Yuji
Y
D000818:Animals; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000201:enzymology / Q000517:prevention & control*; D005260:Female; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011720:Pyrazoles / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D014591:Uterine Diseases / Q000201:enzymology / Q000517:prevention & control*; D014599:Uterus / Q000187:drug effects / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D018932:Chemokine CCL2; C104334:FR 167653; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases