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-1β (IL-1β) and tumour necrosis factor-α (TNF-α) 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-1β and TNF-α 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 17β-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-1β- and TNF-α-induced production of proMMP-9. These results suggest that IL-1β and TNF-α are effective up-regulators of proMMP-9 in the tissue remodelling of human myometrium during labour.