Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Front Immunol. 2020 May 5;11:787. doi: 10.3389/fimmu.2020.00787. eCollection 2020.
Macrophage responses contribute to a diverse array of pathologies ranging from infectious disease to sterile inflammation. Polarization of macrophages determines their cellular function within biological processes. Lipin-1 is a phosphatidic acid phosphatase in which its enzymatic activity contributes to macrophage pro-inflammatory responses. Lipin-1 also possesses transcriptional co-regulator activity and whether this activity is required for macrophage polarization is unknown. Using mice that lack only lipin-1 enzymatic activity or both enzymatic and transcriptional coregulator activities from myeloid cells, we investigated the contribution of lipin-1 transcriptional co-regulator function toward macrophage wound healing polarization. Macrophages lacking both lipin-1 activities did not elicit IL-4 mediated gene expression to levels seen in either wild-type or lipin-1 enzymatically deficient macrophages. Furthermore, mice lacking myeloid-associated lipin-1 have impaired full thickness excisional wound healing compared to wild-type mice or mice only lacking lipin-1 enzymatic activity from myeloid cell. Our study provides evidence that lipin-1 transcriptional co-regulatory activity contributes to macrophage polarization and influences wound healing .
巨噬细胞反应导致多种病理状态，从感染性疾病到无菌性炎症。巨噬细胞的极化决定了它们在生物学过程中的细胞功能。脂磷肌醇-1 是一种磷酸脂酶，其酶活性有助于巨噬细胞的促炎反应。脂磷肌醇-1 还具有转录共调节剂活性，但其活性是否对巨噬细胞极化是必需的尚不清楚。使用仅缺乏髓样细胞中脂磷肌醇-1 酶活性或酶和转录核心调节剂活性的小鼠，我们研究了脂磷肌醇-1 转录共调节剂功能对巨噬细胞伤口愈合极化的贡献。缺乏两种脂磷肌醇-1 活性的巨噬细胞不会引起 IL-4 介导的基因表达，其水平与野生型或脂磷肌醇-1 酶缺陷型巨噬细胞相似。此外，与野生型小鼠或仅缺乏髓样细胞中脂磷肌醇-1 酶活性的小鼠相比，缺乏骨髓相关脂磷肌醇-1 的小鼠在全层切开性创面愈合方面存在缺陷。我们的研究提供了证据，表明脂磷肌醇-1 转录共调节剂活性有助于巨噬细胞极化，并影响伤口愈合。
