Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus.

Elevated Expression and Pro-Inflammatory Activity of IL-36 in Patients with Systemic Lupus Erythematosus.
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DOI:
10.3390/molecules201019588
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发表时间:
2015-10-27
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Tam LS
Tam LS
中科院分区:
其他
文献类型:
--
作者:
Chu M;Wong CK;Cai Z;Dong J;Jiao D;Kam NW;Lam CW;Tam LS

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我们研究了白细胞介素(IL)-36在系统性红斑狼疮(SLE)患者中的表达和促炎活性。采用ELISA和流式细胞术研究了43例SLE患者和16例正常人外周血IL-36及其可能受体的表达水平和CD19+CD24highCD27+调节性B (Breg)淋巴细胞的表达频率。采用Luminex多效法测定重组IL-36刺激外周血单个核细胞(PBMC)血浆细胞因子/趋化因子和体外细胞因子/趋化因子的产生。活动期SLE患者血浆IL-36α、IL-36γ浓度及循环il - 36r阳性CD19+ B淋巴细胞占总B淋巴细胞和PBMC的比例均显著高于对照组(p < 0.05)。血浆IL-36α和IL-36γ与SLE疾病活动性和血浆IL-10浓度升高呈正相关(均p < 0.05)。非活动性和活动性SLE患者外周血中Breg淋巴细胞占总B淋巴细胞和PBMC的频率均较NC患者明显降低(p < 0.01)。Breg淋巴细胞占总B淋巴细胞的频率与il - 36r阳性B淋巴细胞比例呈负相关(p < 0.05)。IL-36α通过诱导IL-6和CXCL8的产生,在SLE患者PBMC中发挥了显著的促炎作用。在IL-36α和IL-36γ刺激下,SLE患者体内IL-6和CXCL8的产生明显高于NC(均p < 0.05)。横断面研究表明,循环IL-36α的过表达可能具有促炎作用,正如在人类SLE中观察到的那样。
We investigated the expression and proinflammatory activity of interleukin (IL)-36 in patients with systemic lupus erythematosus (SLE). The expression level of IL-36, its putative receptors and the frequency of CD19+CD24highCD27+ regulatory B (Breg) lymphocytes of peripheral blood from 43 SLE patients and 16 normal control (NC) subjects were studied using ELISA and flow cytometry. Plasma cytokines/chemokines and ex vivo productions of cytokine/chemokine from peripheral blood mononuclear cells (PBMC) stimulated with recombinant IL-36 were determined by Luminex multiplex assay. Plasma concentrations of IL-36α, IL-36γ and the proportions of circulating IL-36R-positive CD19+ B lymphocytes in total B lymphocytes and PBMC were significantly increased in active SLE patients compared with NC (all p < 0.05). Plasma IL-36α and IL-36γ correlated positively with SLE disease activity and elevated plasma IL-10 concentration (all p < 0.05). The frequencies of circulating Breg lymphocytes in total B lymphocytes and PBMC were significantly decreased in both inactive and active SLE patients compared with NC (all p < 0.01). The frequency of Breg lymphocytes in total B lymphocytes correlated negatively with the proportion of IL-36R-positive B lymphocytes (p < 0.05). IL-36α exerted substantial proinflammatory effect in PBMC from SLE patients by inducing the production of IL-6 and CXCL8. Upon stimulation with IL-36α and IL-36γ, ex vivo productions of IL-6 and CXCL8 were significantly increased in SLE patients compared with NC (all p < 0.05). This cross-sectional study demonstrated that over expression of circulating IL-36α may exert a proinflammatory effect as observed in human SLE.
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