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 metalloproteinase 9 (MMP-9), as a major contributor of tissue remodelling, in human myometrium at parturition. The regulation of proMMP-9 by interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) was also investigated in human myometrial smooth muscle cells. MMP-9 was present in myometrial smooth muscle cells, interstitial fibroblasts and inflammatory cells. The gelatinolytic activities of proMMP-9 in myometrium increased dramatically during labour. IL-1beta and TNF-alpha induced proMMP-9 in myometrial smooth muscle cells, but these effects did not seem to be mediated by protein kinase C. On the other hand, neither 17beta-oestradiol nor progesterone itself affected proMMP-9 production in myometrial smooth muscle cells. Moreover, progesterone, which is known as a physiological suppressor of MMP-9 in other species, did not decrease the IL-1beta- and TNF-alpha-induced production of proMMP-9. These results suggest that IL-1beta and TNF-alpha are effective up-regulators of proMMP-9 in the tissue remodelling of human myometrium during labour.