Department of Surgery, IU Health Comprehensive Wound Center, Indiana Center for Regenerative Medicine and Engineering, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Comprehensive Wound Center and Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.
Sci Rep. 2019 Oct 4;9(1):14293. doi: 10.1038/s41598-019-49435-z.
Collagen containing wound-care dressings are extensively used. However, the mechanism of action of these dressings remain unclear. Earlier studies utilizing a modified collagen gel (MCG) dressing demonstrated improved vascularization of ischemic wounds and better healing outcomes. Wound macrophages are pivotal in facilitating wound angiogenesis and timely healing. The current study was designed to investigate the effect of MCG on wound macrophage phenotype and function. MCG augmented recruitment of macrophage at the wound-site, attenuated pro-inflammatory and promoted anti-inflammatory macrophage polarization. Additionally, MCG increased anti-inflammatory IL-10, IL-4 and pro-angiogenic VEGF production, indicating a direct role of MCG in resolving wound inflammation and improving angiogenesis. At the wound-site, impairment in clearance of apoptotic cell bioburden enables chronic inflammation. Engulfment of apoptotic cells by macrophages (efferocytosis) resolves inflammation via a miR-21-PDCD4-IL-10 pathway. MCG-treated wound macrophages exhibited a significantly bolstered efferocytosis index. Such favorable outcome significantly induced miR-21 expression. MCG-mediated IL-10 production was dampened under conditions of miR-21 knockdown pointing towards miR-21 as a causative factor. Pharmacological inhibition of JNK attenuated IL-10 production by MCG, implicating miR-21-JNK pathway in MCG-mediated IL-10 production by macrophages. This work provides direct evidence demonstrating that a collagen-based wound-care dressing may influence wound macrophage function and therefore modify wound inflammation outcomes.
含胶原蛋白的伤口护理敷料被广泛应用。然而，这些敷料的作用机制尚不清楚。早期研究利用改良胶原蛋白凝胶（MCG）敷料，证明其可改善缺血性伤口的血管生成和更好的愈合效果。伤口巨噬细胞在促进伤口血管生成和及时愈合方面起着关键作用。本研究旨在探讨 MCG 对伤口巨噬细胞表型和功能的影响。MCG 增加了巨噬细胞在伤口部位的募集，减弱了促炎作用，并促进了抗炎极化。此外，MCG 增加了抗炎性的 IL-10、IL-4 和促血管生成的 VEGF 产生，表明 MCG 直接参与解决伤口炎症和改善血管生成。在伤口部位，清除凋亡细胞生物负荷的能力受损会导致慢性炎症。巨噬细胞吞噬凋亡细胞（胞葬作用）通过 miR-21-PDCD4-IL-10 途径解决炎症。MCG 处理的伤口巨噬细胞表现出明显增强的胞葬作用指数。这种有利的结果显著诱导了 miR-21 的表达。在 miR-21 敲低的情况下，MCG 介导的 IL-10 产生被抑制，这表明 miR-21 是一个因果因素。JNK 的药理学抑制减弱了 MCG 诱导的 IL-10 产生，表明 miR-21-JNK 通路在 MCG 介导的巨噬细胞 IL-10 产生中起作用。这项工作提供了直接证据，证明基于胶原蛋白的伤口护理敷料可能影响伤口巨噬细胞的功能，并因此改变伤口炎症的结果。
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