The effect of IL-1β on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes
The effect of IL-1β on the expression of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in human chondrocytes
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DOI：
10.1016/j.lfs.2005.05.052
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发表时间：
2005-11-04
期刊：
影响因子：
6.1
通讯作者：
Matsumura, H
中科院分区：
文献类型：
--
作者：
Aida, Y;Maeno, M;Matsumura, H
白细胞介素-1（IL-1）在改变软骨基质周转中起关键作用。这种周转受基质金属蛋白酶（MMP）和基质金属蛋白酶组织抑制剂（TIMP）的调节。在本研究中，我们研究了IL-1 β对细胞增殖，碱性磷酸酶（ALP）活性，以及MMPs和TIMPs在来自正常人股骨软骨的软骨细胞中的表达的影响。将细胞在含有15%胎牛血清和0、1、10或100 U/ml IL-1 β的Dulbecco改良Eagle培养基中培养长达28天。通过使用实时PCR测定mRNA水平和通过使用酶联免疫吸附测定测定蛋白质水平来估计MMPs和TIMPs的表达水平。培养21天后，在IL-1 β存在下细胞增殖降低。培养第10天后，在IL-1 β存在下，ALT活性显著降低。在IL-1 β存在下，培养21天后MMP-1、MMP-2和MMP-3的表达显著增加。在IL-1 β p存在下，MMP-13的表达在培养的第1d显著增加，但在第7天后显著降低。TIMP-1的表达在培养第14天明显增加。TIMP-2的表达在培养第1天明显下降，但在培养第3 ~ 14天明显升高。这些结果表明，IL-1 β可能主要通过增加细胞产生MMP-13来刺激软骨基质周转。(c)2005年爱思唯尔公司All rights reserved.
Interleukin-1 (IL-1) plays key roles in altering cartilage matrix turnover. This turnover is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). In the present study, we examined the effect of IL-1 beta on cell proliferation, alkaline phosphatase (ALPase) activity, and the expression of MMPs, and TIMPs in chondrocytes derived from normal human femoral cartilage. The cells were cultured in Dulbecco's modified Eagle's medium containing 15% fetal bovine serum and 0, 1, 10, or 100 U/ml of IL-1 beta for up to 28 days. The level of expression of MMPs and TIMPs was estimated by determining mRNA levels using real-time PCR and by determining protein levels using an enzyme-linked immunosorbent assay. Cell proliferation decreased in the presence of IL-1 p after day 21 of culture. ALPase activity decreased significantly in the presence of IL-1 beta after day 10 of culture. The expression of MMP-1, -2, and -3 increased markedly in the presence of IL-1 beta after day 21 of culture. MMP-13 expression increased markedly in the presence of IL-1 beta p on day 1of culture, but decreased markedly after day 7. The expression of TIMP-1ncreased significantly after day 14 of culture. The expression of TIMP-2 decreased significantly on day 1, but increased significantly from day 3 to day 14 of culture. These results suggest that IL-1 beta may stimulate cartilage matrix turnover by increasing mainly MMP-13 production by the cells. (c) 2005 Elsevier Inc. All rights reserved.