Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis

Abstract Equine endometrosis (endometrial fibrosis) is a degenerative chronic process that occurs in the uterus of the mare and disturbs proper endometrial function. Fibrosis is attributed to excessive deposition of extracellular matrix (ECM) components. The turnover of ECM is mediated by matrix metallopeptidases (MMP). Previously, it was shown that cytokines modulate MMP expression in other tissues and may regulate fibrosis indirectly by attracting inflammatory cells to the site of inflammation and directly on various tissues. However, the regulation of MMP expression in equine endometrosis is still relatively unknown. Thus, our aim was to determine if interleukin (IL)-1β and IL-6 regulate ECM, MMPs, or their inhibitors (TIMPs) and whether this regulation differs during endometrosis in the mare. Endometrial fibrosis was divided into four categories according to severity: I (no degenerative changes), IIA (mild degenerative changes), IIB (moderate degenerative changes) and III (severe degenerative changes) according to Kenney and Doig classification. Endometrial explants (n = 5 for category I, IIA, IIB and III according to Kenney and Doig) were incubated with IL-1β (10 ng/ml) or IL-6 (10 ng/ml) for 24 h. Secretion and mRNA transcription of collagen type 1 ( Col1a1) and type 3 ( Col3a1) , fibronectin ( Fn1 ), Mmp-1, -2 , -3 , -9 , -13 , Timp-1 , -2 were analyzed by real-time PCR and ELISA, respectively. IL-1β treatment up-regulated secretion of COL1, MMP-2, TIMP1, and TIMP2 in category I endometrial fibrosis tissues (P