title: Inhibition by medroxyprogesterone acetate of interleukin-1β-induced collagen degradation by corneal fibroblasts.
abstract: OBJECTIVE
  To examine the effect of medroxyprogesterone 17-acetate (MPA) on interleukin-1β (IL-1β)-induced collagen degradation by corneal fibroblasts.
  
  
  METHODS
  Rabbit corneal fibroblasts were cultured in three-dimensional collagen gels with or without MPA. Collagen degradation was determined by measurement of hydroxyproline after acid hydrolysis. The expression or activity of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) was evaluated by immunoblot analysis or gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) in corneal fibroblasts was examined by immunoblot analysis. Cell proliferation and viability were evaluated by measurement of bromodeoxyuridine incorporation and the release of lactate dehydrogenase, respectively.
  
  
  RESULTS
  MPA inhibited IL-1β-induced collagen degradation by corneal fibroblasts in a concentration- and time-dependent manner. MMP expression and activation as well as TIMP expression in corneal fibroblasts exposed to IL-1β were also inhibited by MPA. MPA had no effect on cell proliferation or viability. MPA inhibited the IL-1β-induced phosphorylation of p38 MAPK without affecting that of the MAPKs ERK or JNK. IL-1β-induced MMP expression and activation as well as collagen degradation were also blocked by the p38 MAPK inhibitor SB203580.
  
  
  CONCLUSIONS
  MPA inhibited MMP expression and thereby suppressed collagen degradation by corneal fibroblasts induced by IL-1β. Furthermore, inhibition of p38 MAPK phosphorylation by MPA may contribute to its inhibition of collagen degradation.
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Orita
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005347:Fibroblasts; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011817:Rabbits; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
chemical_list: D053583:Interleukin-1beta; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D017258:Medroxyprogesterone Acetate; D020782:Matrix Metalloproteinases