Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus

Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus
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DOI:
10.1177/0961203315585815
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发表时间:
2015-10-01
期刊:
影响因子:
2.6
通讯作者:
Tam, L. S.
Tam, L. S.
中科院分区:
医学4区
文献类型:
--
作者:
Cai, Z.;Wong, C. K.;Tam, L. S.

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目的探讨IL-35在系统性红斑狼疮(SLE)发病中的调节作用。方法采用ELISA法检测SLE患者和健康对照者血浆中IL-35和可溶性gp 130的浓度。采用RT-qPCR检测外周血单个核细胞(PBMC)中IL-35亚基(p35和EBI 3)及其受体(gp 130和IL-12 R2)的mRNA表达。采用流式细胞术检测CD 4(+)CD 25(高)CD 127(-)Treg细胞数量及CD 4+辅助(Th)细胞和CD 19 + B细胞上IL-35受体的表达。结果血浆IL-35和可溶性gp 130水平呈正相关,且在重度SLE患者中显著高于HC。SLE患者血浆中炎性细胞因子/趋化因子CCL 2、CXCL 8、IL-6、干扰素(IFN)-、IL-10和IL-17 A的水平显著高于HC。SLE患者PBMC中IL-35及其受体mRNA水平呈显著正相关,且SLE患者PBMC中IL-35及其受体mRNA水平高于HC。这种增加与SLE疾病活动指数(SLEDAI)的变化显著相关(所有p
Objective This study characterizes an IL-35-mediated regulatory role in patients with systemic lupus erythematosus (SLE).Methods Plasma of SLE patients and healthy controls (HCs) was analyzed for the concentrations of IL-35 and soluble gp130 by using ELISA. mRNA expression of IL-35 subunit (p35 and EBI3) and its receptor (gp130 and IL-12R2) in peripheral blood mononuclear cells (PBMCs) was assessed by RT-qPCR. Flow cytometry was performed to evaluate the number of CD4(+)CD25(high)CD127(-)Treg cells and the expression of IL-35 receptor on the CD4+ helper (Th) cells and CD19+ B cells. Plasma collected from SLE patients and HCs was assayed for cytokine and chemokine expression by Luminex multiplex assay.Results Plasma IL-35 and soluble gp130 levels positively correlated with each other and were significantly higher in patients with severe SLE compared with HCs. Significantly higher levels of inflammatory cytokines/chemokines CCL2, CXCL8, IL-6, interferon (IFN)-, IL-10 and IL-17A were observed in plasma of SLE patients than HCs. mRNA levels of IL-35 and its receptor were significantly positively correlated in PBMCs from SLE patients and their levels were higher in SLE than HCs. The increase significantly correlated with changes in SLE Disease Activity Index (SLEDAI) (all p