软骨细胞
一氧化氮合酶
转化生长因子β
BETA(编程语言)
一氧化氮
转化生长因子
转化生长因子β1
内分泌学
内科学
化学
细胞生长
转化生长因子β信号通路
生物
体外
生物化学
医学
计算机科学
程序设计语言
作者
F.J. Blanco,Yi Geng,Martin Lotz
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:1995-04-15
卷期号:154 (8): 4018-4026
被引量:108
标识
DOI:10.4049/jimmunol.154.8.4018
摘要
Abstract This study analyzed the effect of chondrocyte differentiation on iNOS expression and responses to IL-1 and TGF-beta. During subculturing of chondrocytes, the growth-stimulatory effects of TGF-beta decreased, and cells in later passages even were growth inhibited by TGF-beta. IL-1 beta responses showed an inverse pattern. The antiproliferative effects of IL-1 beta decreased, and, after passage 6, IL-1 beta became a growth stimulator for chondrocytes. This change in growth factor response pattern was associated with a decrease in type II collagen expression. To determine whether these changes in the growth regulatory effects of IL-1 beta and TGF-beta were related to nitric oxide (NO), inducible nitric oxide synthase (iNOS) expression and NO release were analyzed. In primary chondrocytes, TGF-beta did not stimulate iNOS mRNA expression or NO release, and, during co-incubation, it did not detectably alter the IL-1 beta effect. Preincubation with TGF-beta resulted in a time-dependent increase in IL-1-induced NO. With increasing passage number, the IL-1 beta effects decreased, and, after passage 6, IL-1 beta no longer detectably stimulated iNOS expression or NO release. However, TGF-beta increased NO production synergistically with IL-1 beta during the same culture period when it lost its growth-stimulatory effects. The antiproliferative effects of TGF-beta in late passage chondrocytes were reversed by the NO synthase inhibitor NG-monomethylarginine. These results suggest a novel pattern of iNOS regulation by IL-1 and TGF-beta and show that the factors that modulate iNOS expression and proliferation are dependent on the differentiation status of the cells.
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