Effects of pro- and anti-inflammatory cytokines and nitric oxide donors on hyaluronic acid synthesis by synovial cells from patients with rheumatoid arthritis
Effects of pro- and anti-inflammatory cytokines and nitric oxide donors on hyaluronic acid synthesis by synovial cells from patients with rheumatoid arthritis
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DOI：
10.1042/cs20040104
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发表时间：
2004-09-01
期刊：
影响因子：
6
通讯作者：
Borderie, D
中科院分区：
文献类型：
--
作者：
Chenevier-Gobeaux, C;Morin-Robinet, S;Borderie, D
本研究旨在探讨促炎症细胞因子IL-1β、肿瘤坏死因子-α、干扰素-γ和抗炎细胞因子IL-4、IL-13和一氧化氮(NO)对类风湿关节炎滑膜细胞产生透明质酸(HA)的影响。将5例类风湿关节炎患者滑膜细胞分别与IL-1β、肿瘤坏死因子-α、干扰素-γ或与IL-4或IL-13混合培养24 h，再与硝普钠或S亚硝基-N-乙酰-DL-青霉胺共同孵育324 h。根据从牛软骨中分离的蛋白多糖与HA的特异性结合，用免疫酶分析法检测HA的分泌。IL-1β、肿瘤坏死因子α和干扰素-γ单独或联合刺激透明质酸合成，而IL-4和IL-13呈剂量依赖性抑制Th1细胞因子诱导的透明质酸合成。1 mM SNP处理6、12 h后，HA产量显著增加(效果最好)。0.01 mM和0.1 mM SNAP处理细胞12h后透明质酸产量显著增加，1 mM SNAP处理细胞24 h后透明质酸产量最高。综上所述，本研究提供了促炎症和抗炎细胞因子以及NO供体对类风湿滑膜细胞HA代谢的调节作用，有助于了解类风湿关节炎的病理生理机制。
The aim of the present study was to investigate the effects of (i) the pro-inflammatory cytokines IL (interleukin)-1beta, TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and anti-inflammatory cytokines IL-4 and IL-13, and (ii) NO (nitric oxide) donors on HA (hyaluronic acid) production by synovial cells from patients with rheumatoid arthritis. Synovial cells obtained from five patients with rheumatoid arthritis were incubated for 24 h without or with IL-1beta, TNF-alpha, IFN-gamma, or with this mixture for 24 h plus IL-4 or IL-13 for the last 6 h. The same cells were also incubated for 324 h without or with SNP (sodium nitroprusside) or SNAP (S-nitroso-N-acetyl-DL-penicillamine). HA secretion was determined by an immunoenzymic assay based on HA-specific binding by proteoglycan isolated from bovine cartilage. IL-1beta, TNF-alpha and IFN-gamma alone or in combination stimulated HA synthesis, whereas IL-4 and IL-13 dose-dependently inhibited HA production induced by Th1 cytokines. HA production was significantly increased by the presence of 1 mM SNP after 6 and 12 h (maximal effect). HA production was significantly increased by the presence of 0.01 and 0.1 mM SNAP after 12 h of incubation, and cells treated with 1 mM SNAP showed a maximal HA production after 24 h of incubation. In conclusion, the present study provides data concerning the regulatory role of pro- and anti-inflammatory cytokines and NO donors on HA metabolism in rheumatoid synovial cells and may help in understanding the pathophysiology of rheumatoid arthritis.