Expression of the Ym2 Lectin-binding Protein Is Dependent on Interleukin (IL)-4 and IL-13 Signal Transduction

Expression of the Ym2 Lectin-binding Protein Is Dependent on Interleukin (IL)-4 and IL-13 Signal Transduction
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Ym2 凝集素结合蛋白的表达依赖于白细胞介素 (IL)-4 和 IL-13 信号转导

DOI:
10.1074/jbc.m106223200
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发表时间:
2001
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
P. Foster
P. Foster
中科院分区:
--
文献类型:
--
作者:
D. Webb;A. McKenzie;P. Foster

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哮喘的病理生理受CD4+Th2淋巴细胞和细胞因子IL-4和IL-13的密切调控。然而,这些细胞因子促进疾病的机制尚未完全阐明。为了寻找新的过敏性分子介质,通过与支气管肺泡灌洗液的比较,证明了YM2蛋白在变态反应发生发展过程中在肺组织中大量上调。也检测到低水平的YM1异构体。重要的是,YM1和YM2以前都没有在过敏性肺部炎症的背景下被描述。Western免疫印迹显示,这些蛋白的表达增强依赖于CD_4+T细胞和IL-4或IL-13通过IL-4Rα亚基的信号转导。此外,将IL-13注入幼稚小鼠的气管内足以诱导表达。YM1与嗜酸性粒细胞趋化因子L同源,但在体外和体内实验中,仅观察到嗜酸性粒细胞对YM蛋白的弱趋化。相比之下,YM1和YM2与组织重塑相关蛋白的同源性,以及先前发现YM1与几丁质酶同源,并与硫酸肝素和GlcN寡聚体(几丁二糖、几丁三糖和几丁糖)结合,强烈表明这些蛋白在过敏性肺的气道壁重建中发挥重要作用。
Asthma pathophysiology is intimately regulated by CD4+ Th2 lymphocytes and the cytokines interleukin (IL)-4 and IL-13. However, the mechanisms by which these cytokines promote disease have not been fully elucidated. In order to identify novel molecular mediators of allergy, a comparison was made of the bronchoalveolar lavage, which demonstrated that the Ym2 protein was abundantly up-regulated in the lung during the development of allergy. Low levels of the Ym1 isomer were also detected. Importantly, neither Ym1 nor Ym2 has been characterized previously in the context of allergic pulmonary inflammation. Western immunoblot showed that enhanced expression of these proteins was dependent on CD4+T cells and IL-4 or IL-13 signaling via the IL-4Rα subunit. In addition, intratracheal instillation of IL-13 into naive mice was sufficient to induce expression. Ym1 is homologous to eosinophil chemotactic factor L. However, only weak eosinophil chemotaxis was observed in response to Ym protein in both in vitro andin vivo assays. By contrast, the homology of Ym1 and Ym2 to proteins associated with tissue remodeling, together with the previous findings that Ym1 is homologous to chitinase and binds heparin sulfate and GlcN oligomers (chitobiose, chitotriose, and chitotetraose), strongly suggests these proteins play an important role in airway wall remodeling in the allergic lung.
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