Department of Pathophysiology, Hainan Medical College, Haikou, Hainan 571101, China.
Cytokine. 2013 Feb;61(2):469-77. doi: 10.1016/j.cyto.2012.10.032. Epub 2012 Dec 5.
Interleukin (IL)-29 is a relatively newly discovered cytokine, which has been shown to be actively involved in the pathogenesis of allergic inflammation. However, little is known of the effects of IL-29 on protease activated receptor (PAR) expression and potential mechanisms of cytokine production in mast cells. In the present study, we examined potential influence of IL-29 on PAR expression and cytokine production in P815 and bone marrow derived mast cells (BMMCs) by using flow cytometry analysis, quantitative real time PCR, and ELISA techniques. The results showed that IL-29 downregulated the expression of PAR-1 by up to 56.2%, but had little influence on the expression of PAR-2, PAR-3 and PAR-4. IL-29 also induced downregulation of expression of PAR-1 mRNA. However, when mast cells were pre-incubated with IL-29, thrombin-, trypsin- and tryptase-induced expression of PAR-2, PAR-3 and PAR-4 was upregulated, respectively. IL-29 provoked approximately up to 1.9-fold increase in IL-4 release when mast cells was challenged with IL-29. Administration of IL-29 blocking antibody, AG490 or LY294002 abolished IL-29-induced IL-4 release from P815 cells. It was found that IL-29 diminished trypsin- and tryptase-induced IL-4 release from P815 cells following 16 h incubation. In conclusion, IL-29 can regulate expression of PARs and tryptase- and trypsin-induced IL-4 production in mast cells, through which participates in the mast cell related inflammation.
白细胞介素 (IL)-29 是一种相对较新发现的细胞因子，已被证明在过敏炎症的发病机制中起积极作用。然而，对于白细胞介素-29 对肥大细胞中蛋白酶激活受体 (PAR) 表达和潜在细胞因子产生机制的影响知之甚少。在本研究中，我们通过流式细胞术分析、实时定量 PCR 和 ELISA 技术，研究了白细胞介素-29 对 P815 和骨髓来源的肥大细胞 (BMMC) 中 PAR 表达和细胞因子产生的潜在影响。结果表明，白细胞介素-29 通过上调将 PAR-1 的表达下调高达 56.2%，但对 PAR-2、PAR-3 和 PAR-4 的表达影响较小。白细胞介素-29 还诱导 PAR-1 mRNA 的表达下调。然而，当肥大细胞预先用白细胞介素-29 孵育时，凝血酶、胰蛋白酶和胰蛋白酶诱导的 PAR-2、PAR-3 和 PAR-4 的表达分别上调。当肥大细胞受到白细胞介素-29 刺激时，白细胞介素-29 可引起 IL-4 释放增加约 1.9 倍。给予白细胞介素-29 阻断抗体 AG490 或 LY294002 可消除 P815 细胞中白细胞介素-29 诱导的 IL-4 释放。研究发现，白细胞介素-29 可在 16 小时孵育后降低胰蛋白酶和胰蛋白酶诱导的 P815 细胞中 IL-4 的释放。综上所述，白细胞介素-29 可调节肥大细胞中 PARs 的表达和胰蛋白酶和胰蛋白酶诱导的 IL-4 产生，从而参与与肥大细胞相关的炎症反应。
