Resistin-like molecule alpha (RELMα) and YM-1 are secreted proteins implicated in murine models of alternatively activated macrophage (AA/M2) accumulation and Th2-skewed inflammation. Since the gp130 cytokine Oncostatin M (OSM) induces a Th2-like cytokine and AA/M2 skewed inflammation in mouse lung, we here investigated regulation of RELMα and YM-1. Transient pulmonary overexpression of OSM by Adenovirus vector (AdOSM) markedly induced RELMα and YM-1 protein expression in total lung. In situ hybridization showed that RELMα mRNA was highly induced in airway epithelial cells (AEC) and was co-expressed with CD68 mRNA in some but not all CD68+ cells in parenchyma. IL-6 overexpression (a comparator gp130 cytokine) induced RELMα, but at significantly lower levels. IL-6 (assessing IL-6^−/− mice) was not required, nor was STAT6 (IL-4/13 canonical signalling) for AdOSM-induction of RELMα in AEC. AEC responded directly to OSM in vitro as assessed by pSTAT3 activation. RELMα-deficient mice showed similar inflammatory cell infiltration and cytokine responses to wt in response to AdOSM, but showed less accumulation of CD206+ AA/M2 macrophages, reduced induction of extracellular matrix gene mRNAs for COL1A1, COL3A1, MMP13, and TIMP1, and reduced parenchymal alpha smooth muscle actin. Thus, RELMα is regulated by OSM in AEC and contributes to extracellular matrix remodelling in mouse lung.

中文翻译：

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在小鼠肺活体内，通过抑瘤素M可以在呼吸道上皮细胞中诱导RELMα，而无需STAT6或IL-6。

抵抗素样分子α（RELMα）和YM-1是涉及交替激活的巨噬细胞（AA / M2）积累和Th2偏向炎症的小鼠模型的分泌蛋白。由于gp130细胞因子Oncostatin M（OSM）诱导了Th2样细胞因子，AA / M2偏向小鼠肺部发炎，因此我们在这里研究了RELMα和YM-1的调节。腺病毒载体（AdOSM）瞬时使OSM肺过度表达明显诱导了全肺中RELMα和YM-1蛋白的表达。原位杂交表明RELMαmRNA在气道上皮细胞（AEC）中被高度诱导，并在实质中的一些但不是全部CD68 +细胞中与CD68 mRNA共表达。IL-6过表达（比较物gp130细胞因子）诱导RELMα，但水平明显降低。IL-6（评估IL-6 ^{- / -}AEC中，AdOSM诱导RELMα的STAT6（IL-4 / 13规范信号）也不需要。通过pSTAT3激活评估，AEC在体外直接对OSM有反应。缺乏RELMα的小鼠表现出相似的炎症细胞浸润和细胞因子对wt的响应，响应AdOSM，但显示出CD206 + AA / M2巨噬细胞的积累减少，COL1A1，COL3A1，MMP13和TIMP1的细胞外基质基因mRNA诱导减少，实质减少α平滑肌肌动蛋白。因此，RELMα在AEC中受OSM调控，并有助于小鼠肺中的细胞外基质重塑。