IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation
IL-25 regulates the expression of adhesion molecules on eosinophils: mechanism of eosinophilia in allergic inflammation
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DOI：
10.1111/j.1398-9995.2006.01102.x
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发表时间：
2006-07-01
期刊：
影响因子：
12.4
通讯作者：
Lam, CWK
中科院分区：
文献类型：
--
作者：
Cheung, PFY;Wong, CK;Lam, CWK
背景：白介素25(IL-25)是一种新的T辅助细胞因子，属于IL-17家族，在变态反应性炎症中起关键作用。最近的研究报道，IL-25在小鼠体内过表达可导致嗜酸性粒细胞增多。我们研究了IL-25对人嗜酸性粒细胞表面几种黏附分子表达的影响及其细胞内机制。方法：采用膜联蛋白V-异硫氰酸荧光素(FITC)法检测嗜酸性粒细胞活性。用逆转录聚合酶链式反应(RT-PCR)和流式细胞术分别检测嗜酸性粒细胞表面细胞间黏附分子-1(CD54)、细胞间黏附分子-3(CD50)、L选择素(CD62L)、白细胞功能相关抗原(CD11a/CD18)和极晚期抗原-4(VLA-4、CD49d/CD29)的基因表达和表面表达。结果：IL-25可剂量依赖性地提高嗜酸性粒细胞活性，从41%增加到76%。IL-25可明显上调嗜酸性粒细胞表面ICAM-1的表达，抑制ICAM-3和L-选择素的表达，并呈剂量依赖关系。IL-25还显著增强了嗜酸性粒细胞与纤维连接蛋白的粘附性。此外，p38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580、C-Jun氨基末端蛋白激酶(JNK)抑制剂SP600125和蛋白酶体抑制剂MG-132可显著抑制IL-25诱导的L-选择素、细胞间黏附分子-1和细胞间黏附分子-3的表达以及嗜酸性粒细胞与纤维连接蛋白的黏附(均P<；结论：IL-25通过激活p38MAPK、JNK和核因子-kappaB通路，促进人嗜酸性粒细胞存活，调节细胞间黏附分子-1、细胞间黏附分子-3和L-选择素的表面表达，从而揭示了IL-25诱导的变态反应性炎症嗜酸性粒细胞增多症的分子机制。
Background: Interleukin-25 (IL-25) is a novel T-helper-2 (Th2) cytokine of the IL-17 family that plays a key role in allergic inflammation. Recent studies reported that over-expression of IL-25 in mouse induces eosinophilia. We investigated the effect of IL-25 on the expression of several adhesion molecules on human eosinophils and the underlying intracellular mechanisms.Methods: Viability of eosinophils was measured by annexin V-flourescein isothiocyanate (FITC) assay. Gene expression and surface expression of intercellular adhesion molecule (ICAM)-1 (CD54), ICAM-3 (CD50), L-selectin (CD62L), leukocyte function-associated antigen (LFA-1) (CD11a/CD18) and very late antigen-4 (VLA-4, CD49d/CD29) on eosinophils were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, respectively. Adhesion of eosinophils to fibronectin was assessed using the fibronectin-coated insert system.Results: Viability of eosinophils was significantly enhanced by IL-25 from 41% to 76% dose-dependently. IL-25 could significantly upregulate the surface expression of ICAM-1, but suppress those of ICAM-3 and L-selectin on eosinophils in a dose-dependent manner. Adhesion of eosinophils to fibronectin was also significantly enhanced by IL-25. Besides, pre-incubation with p38 mitogen-activated protein kinases (MAPK) inhibitor SB203580, C-Jun NH2-terminal protein kinases (JNK) inhibitor SP600125 and proteosome inhibitor MG-132 could significantly restrain the effects of IL-25 on surface expression of L-selectin, ICAM-1 and ICAM-3, respectively, and also on the adhesion of eosinophils onto fibronectin (all P < 0.05).Conclusions: Our findings suggest an essential role of IL-25 in enhancing survival and regulating surface expression of ICAM-1, ICAM-3 and L-selectin on human eosinophils through the activation of p38 MAPK, JNK and nuclear factor (NF)-kappa B pathways, thereby shedding light on the molecular mechanisms of IL-25-induced eosinophilia in allergic inflammation.