IL-1ra对IL-1α诱导的眼眶成纤维细胞合成糖胺多糖的抑制作用

IL-1ra inhibits IL-1α-induced glycosaminoglycans production in cultured orbital fibroblasts

目的 :明确白介素 1受体拮抗剂 (IL 1ra)是否对白介素 1α(IL 1α)诱导的眼眶成纤维细胞合成糖胺多糖 (gly cosaminoglycans,GAG)有抑制作用 ,探讨IL 1ra在Graves’眼病(GO)治疗及预防中的临床应用前景。方法 :以下述方法分别处理培养的GO患者和正常人眼眶成纤维细胞 :IL 1α 30U/ml或 /和不同浓度的IL 1ra孵育 4 8h ;用IL 1α 30U/ml处理后 ,再加入IL 1ra 75ng/ml共孵育不同时间 (2 4h、4 8h、72h)。用 [3 H]葡萄糖胺掺入法测定 [3 H]GAG的产量。结果IL 1α 30U/ml明显刺激GO患者和正常人成纤维细胞合成GAG ,增加率达 4 6 .6 %～ 12 7.9% (平均 10 3.5 % ,P <0 .0 0 1)。与IL 1α 30U/ml克分子浓度比为 2 5∶1、4 0∶1和 10 0∶1的IL 1ra ,分别抑制IL 1α诱导的GO患者和正常人成纤维细胞合成GAG达 (30 .93± 11.4 6 ) %、(5 9.34± 9.3) %和 (83.15± 8.5 6 ) % (P <0 .0 0 5 )。在 2 4h、4 8h、72h时 ,IL 1ra分别抑制IL 1α诱导的眼眶成纤维细胞合成GAG(2 4 .18± 6 .3) %、(6 0 .4 8± 12 .83) %和 (73.0 4± 7.14 ) % (前两组相比 ,P <0 .0 0 1;后两组相比 ,P =0 .15 9)。结论 :IL 1ra能够剂量和时间依赖性地抑制IL 1α诱导的眼眶成纤维细胞合成GAG ,IL 1ra可望用于GO的治疗和预防。

Objective:To identify whether the interleukin-1 receptor antagonist(IL-1ra) inhibits interleukin-1α(IL-1α)-induced glycosaminoglycans(GAG) production in cultured orbital fibroblasts.Methods:Different concentrations of IL-1ra or/and IL-1α 30 U/ml for 48 h;IL-1ra 75 ng/ml and IL-1α 30 U/ml for 24～72 h were used to challenge cultured orbital fibroblasts in patients with GO and in controls. Cells were labeled with glucosamine for GAG quantification.Results:IL-1α 30 U/ml stimulated GAG synthesis by 46.6%～127.9%(mean,103.5%;P<0.001) in orbital fibroblasts from both GO patients and controls. Treatment with IL-1ra at concentrations of 25-fold,40-fold,and 100-fold molar excess:IL-1α-stimulated GAG production was significantly inhibited by (30.93±11.46)%,(59.34±9.3)% and (83.15±8.56)%,respectively(P<0.005). Treatment with IL-1ra 75 ng/ml for 24 h,48 h,and 72 h:IL-1α-stimulated GAG synthesis was inhibited by (24.18±6.3)%,(60.48±12.83)% and (73.04±7.14)%,respectively(the former two groups,P<0.001,the latter two groups,P=0.159).Conclusion:IL-1ra inhibits IL-1α-induced GAG production in cultured orbital fibroblasts in dose-and time-dependent manners. IL-1ra may be useful in the prevention or treatment of GO.