Resistin-like molecule-β is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung
Resistin-like molecule-β is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung
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DOI：
10.1152/ajplung.00147.2007
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发表时间：
2007-08-01
影响因子：
4.9
通讯作者：
Rothenberg, Marc E.
中科院分区：
文献类型：
--
作者：
Mishra, Anil;Wang, Meiqin;Rothenberg, Marc E.
抵抗素样分子(RELM)-β是一种富含半胱氨酸的细胞因子，与胰岛素抵抗和哮喘反应有关，但其功能仍是一个谜。我们现在报道，RELM-beta在促进小鼠肺的呼吸道炎症和肺重塑方面起到了作用。多种过敏原和辅助性T细胞因子2(Th2)通过依赖IL-13和STAT6的机制强烈诱导RELM-β。为了了解RELm-beta在体内的作用，我们将重组小鼠的RELm-beta经气管注入幼鼠体内。RELm-beta诱导剂量依赖的白细胞聚集(最明显的累及巨噬细胞)和杯状细胞增生。RELM-β诱导的最显著作用是增加血管周围和支气管周围的胶原沉积。在过敏性呼吸道炎症的实验模型中，RELM-β基因缺陷的小鼠减少了胶原的积累和杯状细胞的增殖。体外实验证明，RELM-β具有成纤维细胞的促成纤维细胞活性。这些结果表明，RELM-β是一种与Th2相关的细胞因子，具有强大的炎症和重塑活性。
Resistin-like molecule (RELM)-beta is a cysteine-rich cytokine implicated in insulin resistance and asthmatic responses, but its function remains an enigma. We now report that RELM-beta has a role in promoting airway inflammation and lung remodeling in the mouse lung. RELM-beta is strongly induced by diverse allergens and T helper type 2 (Th2) cytokines by an IL-13- and STAT6-dependent mechanism. To understand the in vivo role of RELM-beta we delivered recombinant murine RELM-beta intratracheally to naive mice. RELM-beta induced dose-dependent leukocyte accumulation (most prominently involving macrophages) and goblet cell hyperplasia. The most prominent effect induced by RELM-beta was increased perivascular and peribronchial collagen deposition. Mice genetically deficient in RELM-beta had reduced accumulation of collagen and goblet cell hyperplasia in an experimental model of allergic airway inflammation. In vitro experiments demonstrated that RELM-beta had fibroblast motogenic activity. These results identify RELM-beta as a Th2-associated cytokine with potent inflammatory and remodeling activity.