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首页> 外文期刊>Allergy >CRTH2 mediates the activation of human Th2 cells in response to PGD_2 released from IgE/anti-lgE treated nasal polyp tissue
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CRTH2 mediates the activation of human Th2 cells in response to PGD_2 released from IgE/anti-lgE treated nasal polyp tissue

机译:CRTH2介导人类Th2细胞的激活,以响应从IgE /抗lgE处理的鼻息肉组织释放的PGD_2

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Background: Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D_2 (PGD_2) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue.Methods: Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti-lgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD_2. Supernatants were assayed for PGD_2 content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DPi), chemoattractant receptor-homologous receptor expressed on Th2 cells (CRTH2) and PGD_2 synthase were analysed by real time PCR.Results: Increased release of PGD_2 by nasal polyp tissue treated with IgE/anti-lgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD_2 synthase, DP_1 and CRTH2 receptors increased after stimulation with IgE/anti-lgE. Supernatants from IgE/anti-IgE-stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD_2 produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. Conclusion: These data suggest that in immunologically activated nasal polyp tissue, PGD2 produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism.
机译:背景:肥大细胞在刺激后释放介体,从而导致慢性气道疾病的发病机理,包括Th2淋巴细胞的募集和激活。目的是通过鼻息肉组织确定前列腺素D_2(PGD_2)及其受体在Th2细胞趋化性中的参与。方法:将10例鼻息肉患者的组织外植体与单独的RPMI或含IgE / anti- lgE 30分钟。一些样品用双氯芬酸处理以抑制PGD_2的产生。在存在和不存在CRTH2拮抗剂的情况下,测定上清液的PGD_2含量及其促进人Th2细胞趋化性的能力。实时荧光定量PCR分析了Th2细胞上表达的D类前列腺素受体1型(DPi),趋化性受体-同源受体(CRTH2)和PGD_2合酶的转录水平。结果:IgE / anti-用双氯芬酸预温育组织可显着抑制IgE。 IgE /抗IgE刺激后,PGD_2合酶,DP_1和CRTH2受体的转录水平升高。来自IgE /抗IgE刺激的鼻息肉组织的上清液导致Th2细胞趋化性显着提高。产生的PGD_2的水平与Th2细胞趋化程度高度相关。双氯芬酸抑制Th2细胞趋化活性的产生,CRTH2拮抗剂雷马曲班抑制上清液对Th2细胞的趋化作用。结论:这些数据表明,在免疫激活的鼻息肉组织中,肥大细胞产生的PGD2通过CRTH2依赖性机制促进Th2细胞的迁移。

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