Myeloid‐related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow‐derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest‐specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M₂‐ to M₁‐like phenotype by upregulating expression of M₁‐related surface receptor proteins and signature M₁‐marker genes and by downregulating signature M₂‐marker gene expression, which depends on Toll‐like receptor 4 and p38 mitogen‐activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14‐mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.

中文翻译：

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MRP8/14 通过 RAGE 和 Gas6/MFG-E8 介导巨噬细胞胞吞作用，并通过 TLR4 依赖性途径诱导极化

髓样相关蛋白 8/14 (MRP8/14) 参与各种炎症反应，然而，其对巨噬细胞胞吞作用的影响尚不清楚。在这里，我们证明 MRP8/14 显着抑制小鼠骨髓源性巨噬细胞 (BMDMs) 对凋亡胸腺细胞的胞吞作用，后来证明这与晚期糖基化终产物 (RAGE) 受体或降低生长表达有关逮捕特异性蛋白 6 和乳脂肪球表皮生长因子 8，独立于 RAGE。此外，MRP8/14通过上调 M ₁相关表面受体蛋白和特征 M _{1 的}表达，促进 BMDMs 从 M ₂到 M ₁样表型的极化标记基因并通过下调特征 M ₂标记基因表达，这取决于 Toll 样受体 4 和 p38 丝裂原活化蛋白激酶/核因子 κB 通路。因此，我们报告了 MRP8/14 对巨噬细胞胞吞作用和 MRP8/14 介导的表型极化的显着抑制作用，这可能有助于开发导致炎症消退的新治疗策略。