ABSTRACT
OBJECTIVE: To explore the intracellular signal transduction pathways of IL-1beta and TNF-alpha in inducing matrix metalloproteinase-9 (MMP-9) in human myometrial smooth muscle cells. METHODS: We studied the expression of MMP-9 induced by cytokines (TNF-alpha and IL-1beta) with zymography. The influence of TNF-alpha and IL-1beta on the phosphorylation of Jun N-terminal kinase (JNK) and IkB were studied with immunoblotting for p-JNK and p-IkB. The intranuclear shifting of NF-kB and AP-1 after treatment with TNF-alpha and IL-1beta were evaluated by EMSA. RESULTS: TNF-alpha- and IL-1beta-induced MMP-9 expression was not suppressed by NF-kB inhibitor (CAPE), AP-1 inhibitor (curcumin) and PKC inhibitor (calphostin C) but was inhibited by tyrosine kinase inhibitor (genistein). After treatment of myometrial smooth muscle cells with TNF-alpha and IL-1beta, phosphorylation of JNK and phosphorylation of IkB with degradation of IkB were evidently observed. The intranuclear translocations of NF-kB and AP-1 were strongly enhanced after treatment with TNF-alpha and IL-1 beta as demonstrated in EMSA. CONCLUSION: In myometrial smooth muscle cells, MMP-9 is induced by TNF-alpha and IL-1beta through PKC activation and transcriptional activations of NF-kB and AP-1. Independent of PKC activation, the signaling of TNF-alpha and IL-1beta in the induction of MMP-9 seems to be transmitted by way of either NF-kB or AP-1 activation in myometrial smooth muscle cells.