Mishra Anil, Wang Meiqin, Schlotman James, Nikolaidis Nikolaos M, DeBrosse Charles W, Karow Margaret L, Rothenberg Marc E
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L305-13. doi: 10.1152/ajplung.00147.2007. Epub 2007 Jun 1.
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 naïve 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.
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,但其功能仍是个谜。我们现在报告,RELM-β在促进小鼠肺部气道炎症和肺重塑中起作用。RELM-β由多种变应原和2型辅助性T(Th2)细胞因子通过白细胞介素-13和信号转导及转录激活因子6(STAT6)依赖的机制强烈诱导。为了解RELM-β在体内的作用,我们将重组小鼠RELM-β经气管内给予未接触过抗原的小鼠。RELM-β诱导剂量依赖性白细胞聚集(最显著的是巨噬细胞)和杯状细胞增生。RELM-β诱导的最显著效应是血管周围和支气管周围胶原沉积增加。在过敏性气道炎症实验模型中,RELM-β基因缺陷的小鼠胶原积累减少,杯状细胞增生也减少。体外实验表明,RELM-β具有成纤维细胞促运动活性。这些结果确定RELM-β是一种具有强大炎症和重塑活性的Th2相关细胞因子。