[Cytokine in synovial monocytic cells from rheumatoid arthritis patients].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Huang
Hong-wei
HW
Department of Rheumatology, First Affiliated Hospital, SUN Yat-sen University, Guangzhou, 510080, China.
Ye
Yu-jin
YJ
Zhan
Zhong-ping
ZP
Chen
Dong-ying
DY
Liang
Liu-qin
LQ
Fan
Jin-jin
JJ
Dong
Xiu-qing
XQ
Yang
Xiu-yan
XY
Xu
Han-shi
HS
D000577:Amides / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D000577:Amides; D016207:Cytokines; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C108830:Y 27632; D054460:rho-Associated Kinases