Miyata M, Sato H, Sato H, Sato Y, Kodama E, Kasukawa R
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Japan.
J Rheumatol. 1999 Oct;26(10):2210-4.
To investigate the role of endogenous heat shock protein (HSP) (rat 60 kDa HSP, rHSP 60) in adjuvant arthritis (AA), the expression of rHSP 60 in AA-susceptible Lewis rats and AA-resistant Fisher rats was studied.
The extent of arthritis was assessed by measuring footpad thickness. The proliferative response of mononuclear cells (MNC) to mycobacterial 65 kDa HSP (mHSP 65) was measured by [3H] thymidine incorporation. The messenger RNA for rHSP 60 was quantified by dot blot hybridization in peripheral blood mononuclear cells (PBMNC), splenic MNC (SMNC), and ankle joint synovial membrane (SM).
In Lewis rats: AA developed on Day 14 after immunization with Freund's complete adjuvant. Proliferative responses of PBMNC and SMNC to mHSP 65 were observed on Day 14 and thereafter according to the development of AA. Messenger RNA levels of rHSP 60 in PBMNC, SMNC, and SM did not increase until Day 21. In Fisher rats: AA and proliferative response of MNC to mHSP 65 were not observed throughout the observation period. Messenger RNA levels of rHSP 60 were significantly higher in preimmune Fisher rats than those in preimmune Lewis rats. Messenger RNA levels of rHSP 60 in PBMNC and SMNC increased significantly on Day 7 and decreased to preimmune levels until Day 21.
We propose that elevated levels and rapid elevation of endogenous HSP 60 levels relate to resistance to AA in Fisher rats; however, lower levels and delayed increase of endogenous HSP 60 levels relate to susceptibility to AA in Lewis rats.
研究内源性热休克蛋白(HSP)(大鼠60 kDa热休克蛋白,rHSP 60)在佐剂性关节炎(AA)中的作用,观察rHSP 60在AA易感的Lewis大鼠和AA抗性的Fisher大鼠中的表达情况。
通过测量足垫厚度评估关节炎程度。采用[3H]胸腺嘧啶核苷掺入法检测单核细胞(MNC)对结核分枝杆菌65 kDa热休克蛋白(mHSP 65)的增殖反应。采用斑点杂交法对外周血单核细胞(PBMNC)、脾单核细胞(SMNC)和踝关节滑膜(SM)中的rHSP 60信使核糖核酸进行定量分析。
在Lewis大鼠中:用弗氏完全佐剂免疫后第14天出现AA。随着AA的发展,在第14天及之后观察到PBMNC和SMNC对mHSP 65的增殖反应。PBMNC、SMNC和SM中rHSP 60的信使核糖核酸水平直到第21天才升高。在Fisher大鼠中:在整个观察期内未观察到AA及MNC对mHSP 65的增殖反应。免疫前Fisher大鼠中rHSP 60的信使核糖核酸水平显著高于免疫前Lewis大鼠。PBMNC和SMNC中rHSP 60的信使核糖核酸水平在第7天显著升高,并在第21天降至免疫前水平。
我们认为,内源性HSP 60水平升高及快速升高与Fisher大鼠对AA的抗性有关;然而,内源性HSP 60水平较低及延迟升高与Lewis大鼠对AA的易感性有关。