Data/hora: 11/06/2024 12:45:38

Provedor de dados: 	Brazilian Journal of Medical and Biological Research	
País: 	Brazil	
Título: 	TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner	
Autores: 	Guo,S.-Y.; Shen,X.; Yang,J.; Yuan,J.; Yang,R.-L.; Mao,K.; Zhao,D.-H.; Li,C.-J.	
Data: 	2007-05-01	
Ano: 	2007	
Palavras-chave: 	Tissue inhibitor of metalloproteinases-1; Hepatocellular carcinoma; Interleukin-6; STAT3; P21.	
Resumo: 	The tissue inhibitor of metalloproteinases (TIMP)-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs) but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line), L-02 (a normal liver cell line) and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma) using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13- and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6) (100 ng/mL) could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclin-dependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.	
Tipo: 	Info:eu-repo/semantics/article	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000500004	
Editor: 	Associação Brasileira de Divulgação Científica	
Relação: 	10.1590/S0100-879X2006005000084	
Formato: 	text/html	
Fonte: 	Brazilian Journal of Medical and Biological Research  v.40 n.5 2007	
Fonte: 	info:eu-repo/semantics/openAccess