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임신 중 자궁 근세포 내에서 cytokine들이 matrix metalloproteinase-9 을 발현시키는 신호전달체계에 관한 연구
서용수(Yong Soo Seo),백금희(Geum Hee Baek),허지희(Ji Hee Heo),양순하(Soon Ha Yang),김종화(Jong Hwa Kim),배덕수(Duk Soo Bae),노정래(Cheong Rae Roh) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5
Objective : To explore the intracellular signal transduction pathways of IL-1β and TNF-α 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-α and IL-1β) with zymography. The influence of TNF-α and IL-1β 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-α and IL-1β were evaluated by EMSA. Results : TNF-α- and IL-1β-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-α and IL-1β, 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-α and IL-1β as demonstrated in EMSA. Conclusion : In myometrial smooth muscle cells, MMP-9 is induced by TNF-α and IL-1β through PKC activation and transcriptional activations of NF-kB and AP-1. Independent of PKC activation, the signaling of TNF-α and IL-1β 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.