Macrophages are critical regulators of pulmonary fibrosis. Their plasticity, proximity, and ability to crosstalk with structural cells of the lung make them a key cell type of interest in the regulation of lung fibrosis. Macrophages can express a variety of phenotypes which have been historically represented through an "M1-like" to "M2-like" delineation. In this classification, M1-like macrophages are proinflammatory and have increased phagocytic capacity compared to alternatively activated M2-like macrophages that are profibrotic and are associated with wound healing. Extensive evidence in the field in both patients and animal models align pulmonary fibrosis with M2 macrophages. In this paper, we performed RNAseq to fully characterize M1 vs. M2-skewed bone marrow-derived macrophages (BMDMs) and investigated the profibrotic abilities of M2 BMDM conditioned media (CM) to promote fibroblast migration, proliferation, alveolar epithelial cell (AEC) apoptosis, and mRNA expression of key fibrotic genes in both fibroblasts and in AECs. Although M2 CM-treated fibroblasts had increased migration and M2 CM-treated fibroblasts and AECs had increased expression of profibrotic proteins over M1 CM-treated cells, all differences can be attributed to M2 polarization reagents IL-4 and IL-13 also present in the CM. Collectively, these data suggest that the profibrotic effects associated with M2 macrophage CM in vitro are attributable to effects of polarization cytokines rather than additional factors secreted in response to those polarizing cytokines.

中文翻译：

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M2 巨噬细胞具有独特的转录组，但条件培养基不促进体外肺成纤维细胞或肺泡上皮细胞的促纤维化反应

巨噬细胞是肺纤维化的关键调节因子。它们的可塑性、接近性和与肺结构细胞串扰的能力使它们成为调节肺纤维化的关键细胞类型。巨噬细胞可以表达各种表型，这些表型在历史上通过“M1 样”到“M2 样”描绘来表示。在该分类中，M1 样巨噬细胞是促炎细胞，与替代激活的促纤维化且与伤口愈合相关的 M2 样巨噬细胞相比，具有增强的吞噬能力。患者和动物模型中的大量证据表明肺纤维化与 M2 巨噬细胞一致。在本文中，我们进行了 RNAseq 以充分表征 M1 与 M1 对比。M2-skewed 骨髓衍生巨噬细胞 (BMDMs) 并研究了 M2 BMDM 条件培养基 (CM) 促进成纤维细胞迁移、增殖、肺泡上皮细胞 (AEC) 凋亡和关键纤维化基因在成纤维细胞和成纤维细胞中的 mRNA 表达的促纤维化能力。在 AEC 中。尽管 M2 CM 处理的成纤维细胞增加了迁移，并且 M2 CM 处理的成纤维细胞和 AEC 在 M1 CM 处理的细胞中增加了促纤维化蛋白的表达，但所有差异都可归因于 M2 极化试剂 IL-4 和 IL-13 也存在于厘米。总的来说，这些数据表明，与 M2 巨噬细胞 CM 相关的促纤维化作用可归因于极化细胞因子的影响，而不是响应于那些极化细胞因子而分泌的其他因子。