Signal transduction of cytokines in inducing matrix metalloproteinas-9 in myometrial smooth muscle cells from term pregnant women.
- Author:
Yong Soo SEO
1
;
Geum Hee BAEK
;
Ji Hee HEO
;
Soon Ha YANG
;
Jong Hwa KIM
;
Duk Soo BAE
;
Cheong Rae ROH
Author Information
1. Department of Obstetrics and Gynecology, Sungkyunkwan University School of Medicine, Samsung Medical Center.
- Publication Type:Original Article
- Keywords:
Cytokine;
Matrix metalloproteinase 9;
Muscle;
smooth;
Uterus;
Pregnancy
- MeSH:
Cytokines*;
Female;
Humans;
Immunoblotting;
Interleukin-1beta;
Matrix Metalloproteinase 9;
Muscle, Smooth*;
Myocytes, Smooth Muscle*;
NF-kappa B;
Phosphorylation;
Phosphotransferases;
Pregnancy;
Pregnant Women*;
Protein-Tyrosine Kinases;
Signal Transduction*;
Transcription Factor AP-1;
Tumor Necrosis Factor-alpha;
Uterus
- From:Korean Journal of Obstetrics and Gynecology
2001;44(5):938-945
- CountryRepublic of Korea
- Language:Korean
-
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.