Interleukin-31 induces cytokine and chemokine production from human bronchial epithelial cells through activation of mitogen-activated protein kinase signalling pathways: implications for the allergic response
Interleukin-31 induces cytokine and chemokine production from human bronchial epithelial cells through activation of mitogen-activated protein kinase signalling pathways: implications for the allergic response
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DOI：
10.1111/j.1365-2567.2007.02668.x
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发表时间：
2007-12-01
期刊：
影响因子：
6.4
通讯作者：
Lam, Christopher W. K.
中科院分区：
文献类型：
--
作者：
Ip, Wai K.;Wong, Chun K.;Lam, Christopher W. K.
白细胞介素-31 （IL-31）是一种新的t辅助淋巴细胞衍生的细胞因子，在过敏性皮肤炎症和特应性皮炎中起重要作用。它最近被认为与支气管炎症有关。我们研究了il -31诱导人支气管上皮细胞活化的功能和机制。首先采用实时定量聚合酶链反应和酶联免疫吸附法测定il -31刺激的人支气管上皮BEAS-2B细胞候选细胞因子/趋化因子的基因和蛋白表达。Western blot检测il -31刺激的BEAS-2B细胞中不同丝裂原活化蛋白激酶（MAPKs）的活性。IL-31能显著提高BEAS-2B细胞表皮生长因子（EGF）、血管内皮生长因子（VEGF）和单核细胞趋化蛋白-1 （MCP-1/CCL2）基因和蛋白的表达，且呈时间依赖性和剂量依赖性。在BEAS-2B细胞和嗜酸性粒细胞共培养中，IL-31与IL-4或IL-13联合可进一步促进VEGF和CCL2的产生，而IL-31可协同促进EGF、VEGF、CCL2、IL-6和IL-8的释放。此外，IL-31可激活BEAS-2B细胞的p38 MAPK、细胞外信号调节激酶（ERK）和c-Jun n -末端激酶（JNK）。p38 MAPK （SB203580）、ERK （PD98059）和JNK （SP600125）的选择性抑制剂可以不同程度地抑制EGF、VEGF和CCL2的产生，从而提示MAPK在IL-31功能中发挥作用。综上所述，MAPKs的激活对于IL-31介导的支气管上皮细胞激活至关重要，从而在支气管炎症中提供IL-31的免疫学作用，至少部分通过上皮EGF、VEGF和CCL2的产生。
Interleukin-31 (IL-31) is a novel T-helper-lymphocyte-derived cytokine that plays an important role in allergic skin inflammation and atopic dermatitis. It has recently been implicated in bronchial inflammation. We investigated the functions and mechanisms of IL-31-induced activation of human bronchial epithelial cells. The gene and protein expressions of candidate cytokines/chemokines from IL-31-stimulated human bronchial epithelial BEAS-2B cells were first quantified by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The activity of different mitogen-activated protein kinases (MAPKs) in IL-31-stimulated BEAS-2B cells was assessed by Western blot. The IL-31 could significantly elevate the gene and protein expressions of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1/CCL2) of BEAS-2B cells in both time-dependently and dose-dependently. Combination of IL-31 with either IL-4 or IL-13 further enhanced VEGF and CCL2 production while IL-31 could synergistically augment the release of EGF, VEGF, CCL2, IL-6 and IL-8 in cocultures of BEAS-2B cells and eosinophils. In addition, IL-31 could activate p38 MAPK, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) of BEAS-2B cells. Selective inhibitors of p38 MAPK (SB203580), ERK (PD98059), and JNK (SP600125) could differentially inhibit the production of EGF, VEGF and CCL2, thereby suggesting a role for MAPKs in IL-31 functions. In conclusion, the activation of MAPKs can be crucial for IL-31-mediated activation of bronchial epithelial cells, thereby providing an immunological role for IL-31 in bronchial inflammation, at least partly, via epithelial EGF, VEGF and CCL2 production.