Huang Hong-wei, Ye Yu-jin, Zhan Zhong-ping, Chen Dong-ying, Liang Liu-qin, Fan Jin-jin, Dong Xiu-qing, Yang Xiu-yan, Xu Han-shi
Department of Rheumatology, First Affiliated Hospital, SUN Yat-sen University, Guangzhou, 510080, China.
Zhonghua Yi Xue Za Zhi. 2009 Jul 21;89(27):1881-4.
To evaluate the inhibitory effect of blockade of Rho kinase upon mediating the secretion of proinflammatory cytokine in monocytic cells from rheumatoid arthritis (RA) patients.
Synovial fluid (SF) monocytic cells and peripheral blood monocytes (PB) from active RA patients were treated with TNFalpha or LPS respectively in the presence or absence of a specific ROK inhibitor, Y27632. ROK activity was assessed by Western blot and cytokine secretion measured by ELISA.
Elevated ROK activity was found in synovial fluid monocytic cells from active RA patients. ROK activity was correlated with DAS, an index of disease activity of RA patients. ROK inhibitor Y27632 reduced the secretion of TNFalpha, IL-1beta and IL-6 in RA SF monocytic cells, but had no effect upon the secretion of IL-10, an anti-inflammatory cytokine.
The present study provides novel evidence that ROK mediates the secretion of proinflammatory cytokines in monocytic cells from RA synovial fluids, suggesting a critical role of ROK in macrophage-mediated synovial inflammation of RA. Thus inhibition of ROK may be a new therapeutic target for RA.