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Korean Journal of Obstetrics & Gynecology 2001;44(5):938-945.
Published online May 1, 2001.
Signal transduction of cytokines in inducing matrix metalloproteinas-9 in myometrial smooth muscle cells from term pregnant women.
Yong Soo Seo, Geum Hee Baek, Ji Hee Heo, Soon Ha Yang, Jong Hwa Kim, Duk Soo Bae, Cheong Rae Roh
Department of Obstetrics and Gynecology, Sungkyunkwan University School of Medicine, Samsung Medical Center.
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.
Key Words: Cytokine, Matrix metalloproteinase 9, Muscle, smooth, Uterus, Pregnancy
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