Up-regulation of matrix metalloproteinase-9 in human myometrium during labour: a cytokine-mediated process in uterine smooth muscle cells

The pregnant uterus undergoes dramatic changes of tissue remodelling during the labour and post-partum period. We studied the production of matrix met alloproteinase 9 (MMP-9), as a major contributor of tissue remodelling, in human myometrium at parturition. The regulation of proMMP-9 by interleukin- 1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) was also in vestigated in human myometrial smooth muscle cells. MMP-9 was present in my ometrial smooth muscle cells, interstitial fibroblasts and inflammatory cel ls. The gelatinolytic activities of proMMP-9 in myometrium increased dramat ically during labour. IL-1 beta and TNF-alpha induced proMMP-9 in myometria l smooth muscle cells, but these effects did not seem to be mediated by pro tein kinase C. On the other hand, neither 17 beta-oestradiol nor progestero ne itself affected proMMP-9 production in myometrial smooth muscle cells. M oreover, progesterone, which is known as a physiological suppressor of MMP- 9 in other species, did not decrease the IL-1 beta- and TNF-alpha-induced p roduction of proMMP-9. These results suggest that IL-1 beta and TNF-alpha a re effective up-regulators of proMMP-9 in the tissue remodelling of human m yometrium during labour.