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骨关节炎患者软骨中白细胞介素-1的检测:其在发病机制中可能的自分泌/旁分泌作用

Detection of interleukin-1 in the cartilage of patients with osteoarthritis: a possible autocrine/paracrine role in pathogenesis.

作者信息

Towle C A, Hung H H, Bonassar L J, Treadwell B V, Mangham D C

机构信息

Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114, USA.

出版信息

Osteoarthritis Cartilage. 1997 Sep;5(5):293-300. doi: 10.1016/s1063-4584(97)80008-8.

Abstract

The interleukin-1 (IL-1) cytokines stimulate the synthesis of degradative enzymes in joint tissues and may play a role in the pathological joint destruction in osteoarthritis (OA). In this study, we have used immunohistochemistry and Western blot analysis to identify IL-1 in human OA cartilage. IL-1 alpha and IL-1 beta were evident in chondrocytes at the articular surface, as well as distributed throughout the cartilage. In many specimens, IL-1 beta but not IL-1 alpha was detected as a diffuse staining of the extracellular matrix especially surrounding superficial zone chondrocytes. Although chondrocyte-associated IL-1 alpha and IL-1 beta were detected in most specimens, cartilages exhibiting early osteoarthritic changes had the highest intensity of staining and the highest frequency of positive cells. Western blot analysis revealed intense immunoreactive bands corresponding to the 35 kDa precursor form of IL-1 alpha in all four chondrocyte lysates tested. The processed 18 kDa IL-1 beta species was present in only one of four chondrocyte lysates, and there was no clear evidence of precursor form within these cells. The results of this study indicate increased IL-1 alpha in cartilage showing early degenerative changes, suggesting an autocrine/paracrine role for this cytokine in OA pathogenesis.

摘要

白细胞介素-1(IL-1)细胞因子可刺激关节组织中降解酶的合成,并可能在骨关节炎(OA)的病理性关节破坏中发挥作用。在本研究中,我们使用免疫组织化学和蛋白质印迹分析来鉴定人OA软骨中的IL-1。IL-1α和IL-1β在关节表面的软骨细胞中明显可见,并且分布于整个软骨。在许多标本中,IL-1β而非IL-1α被检测为细胞外基质的弥漫性染色,尤其是在浅表区软骨细胞周围。尽管在大多数标本中都检测到了与软骨细胞相关的IL-1α和IL-1β,但表现出早期骨关节炎变化的软骨具有最高的染色强度和最高的阳性细胞频率。蛋白质印迹分析显示,在所有测试的四种软骨细胞裂解物中,均出现了与IL-1α的35 kDa前体形式相对应的强免疫反应条带。加工后的18 kDa IL-1β仅存在于四种软骨细胞裂解物中的一种中,并且在这些细胞中没有明确的前体形式的证据。本研究结果表明,在显示早期退变变化的软骨中IL-1α增加,提示该细胞因子在OA发病机制中具有自分泌/旁分泌作用。

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