Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.
Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.
复制标题
DOI：
10.1186/1465-9921-14-34
复制
发表时间：
2013-03-13
影响因子：
5.8
通讯作者：
Halwani R
中科院分区：
文献类型：
--
作者：
Al-Muhsen S;Letuve S;Vazquez-Tello A;Pureza MA;Al-Jahdali H;Bahammam AS;Hamid Q;Halwani R
上皮下纤维化是哮喘期间影响支气管气道功能的最关键的结构变化之一。嗜酸性粒细胞已被证明有助于促纤维化细胞因子、TGF-β 和 IL-11 的产生，然而，调节这一过程的机制尚不完全清楚。在本报告中，我们研究了与哮喘期间炎症相关的细胞因子是否可能诱导嗜酸性粒细胞产生促纤维化细胞因子。从 10 名哮喘患者和 10 名正常对照受试者的外周血中分离出嗜酸性粒细胞。用 Th1、Th2 和 Th17 细胞因子刺激嗜酸性粒细胞，并使用实时 PCR 和 ELISA 测定法测定 TGF-β 和 IL-11 的产生。哮喘和健康个体之间嗜酸性粒细胞衍生的 TGF-β 和 IL-11 细胞因子的基础表达水平相当。用 Th1 和 Th2 细胞因子刺激嗜酸性粒细胞不会诱导促纤维化细胞因子的表达。然而，用 Th17 细胞因子刺激嗜酸性粒细胞会导致哮喘患者而非健康个体中 TGF-β 和 IL-11 表达增强。 IL-17 对嗜酸性粒细胞的这种作用依赖于 p38 MAPK 的激活，因为抑制 p38 MAPK（而非其他激酶）的磷酸化会抑制 IL-17 诱导的促纤维化细胞因子的释放。 Th17 细胞因子可能通过增强嗜酸性粒细胞衍生的促纤维化细胞因子的产生而导致哮喘期间的气道纤维化。通过阻断 Th17 细胞因子对嗜酸性粒细胞的作用来防止促纤维化细胞因子的释放，可能有助于控制由 IL-17 驱动的炎症性疾病（例如过敏性和自身免疫性疾病）的纤维化。
Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood. In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines. Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays. The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release. Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.
登录
查看更多内容
影响因子：
4.3
作者：
Barczyk, A;Pierzchala, W;Sozañska, E
通讯作者：
Sozañska, E
DOI：
10.1165/ajrcmb.19.4.3208
发表时间：
1998-10-01
影响因子：
6.4
作者：
Dubois, GR;Schweizer, RC;Bruijnzeel, PLB
通讯作者：
Bruijnzeel, PLB
影响因子：
14.2
作者：
DURHAM, SR;LOEGERING, DA;KAY, AB
通讯作者：
KAY, AB
DOI：
10.1165/ajrcmb.17.3.2733
发表时间：
1997-09-01
影响因子：
6.4
作者：
Minshall, EM;Leung, DYM;Hamid, Q
通讯作者：
Hamid, Q
影响因子：
14.2
作者：
Molet, S;Hamid, Q;Chakir, J
通讯作者：
Chakir, J