Zenmyo M, Hiraoka K, Komiya S, Morimatsu M, Sasaguri Y
Department of Pathology, Kurume University School of Medicine, Japan.
Virchows Arch. 1995;427(4):437-44. doi: 10.1007/BF00199394.
The purpose of this study was to investigate the role of histamine in human rheumatoid synovial fibroblasts in the production of factors responsible for tissue remodelling and cartilage breakdown in rheumatoid arthritis. We examined the effects of histamine of tritiated thymidine incorporation, production of matrix metalloproteinase-1 (MMP-1), histamine H1-receptor expression, phosphoinositide metabolism and intracellular calcium ion concentration ([Ca2+]i) in human rheumatoid synovial fibroblasts. Tritiated thymidine incorporation studies demonstrated that histamine markedly stimulated the proliferation of rheumatoid synovial fibroblasts. Immunofluorescence and Northern blot analyses revealed that proMMP-1 production was also stimulated by histamine. The levels of inositol phosphates and [Ca2+]i in the cells were elevated in response to histamine, indicating that the cells expressed histamine H1-receptors; and Northern blot analysis indicated that these H1-receptors were up-regulated by histamine. In in situ hybridization, large amounts of histamine H1-receptor mRNA were also detected in rheumatoid synovial tissue. These results suggest that the interaction between H1-receptor expression in rheumatoid synovial fibroblasts and histamine secretion by mast cells and macrophages in the affected sites is an important event responsible for tissue remodelling and joint destruction in rheumatoid arthritis.
本研究的目的是调查组胺在人类类风湿性滑膜成纤维细胞中对类风湿性关节炎中负责组织重塑和软骨破坏的因子产生所起的作用。我们检测了组胺对人类风湿性滑膜成纤维细胞中氚标记胸腺嘧啶核苷掺入、基质金属蛋白酶-1（MMP-1）产生、组胺H1受体表达、磷酸肌醇代谢和细胞内钙离子浓度（[Ca2+]i）的影响。氚标记胸腺嘧啶核苷掺入研究表明，组胺显著刺激类风湿性滑膜成纤维细胞的增殖。免疫荧光和Northern印迹分析显示，组胺也刺激前MMP-1的产生。组胺刺激后，细胞中肌醇磷酸和[Ca2+]i水平升高，表明细胞表达组胺H1受体；Northern印迹分析表明，这些H1受体被组胺上调。原位杂交显示，在类风湿性滑膜组织中也检测到大量组胺H1受体mRNA。这些结果表明，类风湿性滑膜成纤维细胞中H1受体表达与肥大细胞和巨噬细胞在病变部位分泌组胺之间的相互作用是类风湿性关节炎中组织重塑和关节破坏的一个重要事件。
