IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1. The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC­1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot. We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells. This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.

中文翻译：

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白细胞介素35通过抑制HMC-1细胞中的MAPKs途径抑制组胺和促炎细胞因子的产生

IL-35是一种新的抗炎细胞因子，属于IL-12家族。肥大细胞作为免疫应答系统中的主要效应细胞之一，在慢性自发性荨麻疹（CSU）的发病机理中起着重要作用。我们的研究旨在探讨IL-35在HMC-1中的抑制作用。通过CCK8，ELISA或RT-PCR研究了IL-35对人肥大细胞系（HMC1）中细胞增殖，细胞因子表达和组胺释放的影响。通过Western Blot检测PMA加A23187诱导的HMC-1细胞中ERK1 / 2，p38和JNK1 / 2的磷酸化水平。我们发现IL-35显着抑制了PMA和A23187刺激的HMC-1细胞的增殖。IL-35还下调激活的HMC-1中组胺的释放以及IL-6和IL-17的mRNA表达。此外，IL-35显着抑制PMA加A23187诱导的HMC-1细胞中ERK1 / 2，p38和JNK1 / 2的磷酸化水平。该研究提供了关于IL-35在活化的HMC-1细胞中的抑制和抗炎作用的初步观察。我们建议IL35可能在CSU的发病机制中发挥抑制作用。