Activation of PPAR-γ induces macrophage polarization and reduces neutrophil migration mediated by heme oxygenase 1
Activation of PPAR-γ induces macrophage polarization and reduces neutrophil migration mediated by heme oxygenase 1
复制标题
DOI：
10.1016/j.intimp.2020.106565
复制
发表时间：
2020-07-01
影响因子：
5.6
通讯作者：
Clemente Napimoga, Juliana Trindade
中科院分区：
文献类型：
--
作者：
Abdalla, Henrique Ballassini;Napimoga, Marcelo Henrique;Clemente Napimoga, Juliana Trindade
过氧化物酶体增殖物激活受体γ（PPAR-gamma）的天然或合成配体代表了用于治疗炎性病症的药理学干预的有趣工具。特别地，PPAR-gamma激活通过减少细胞因子释放和刺激内源性阿片样物质的合成来预防颞下颌关节（TMJ）中的疼痛和炎症。本研究的目的是阐明PPAR-gamma激活是否诱导巨噬细胞极化，抑制炎性细胞因子释放和白细胞募集。此外，我们研究了血红素加氧酶1（HO-1）参与PPAR-gamma激活后的下游事件。我们的研究结果表明，PPAR-gamma激活消融细胞因子释放骨髓衍生的巨噬细胞（BMDM）在体外。15 d-PGJ（2）诱导大鼠巨噬细胞的PPAR-gamma异源二聚体活化，巨噬细胞从M1样细胞向M2样细胞极化。这种反应通过HO-1介导。PPAR-gamma激活减少角叉菜胶诱导的中性粒细胞迁移，这也是HO-1依赖性的。Ca 2 +/钙调素表达在PPAR-gamma激活后没有变化，表明这不是细胞内L-精氨酸/NO/cGMP/K+ATP通道途径激活所必需的。总之，由PPAR-gamma激活诱导的抗炎作用涉及巨噬细胞极化。HO-1表达增加，HO-1活性是抑制中性粒细胞迁移所必需的。
Natural or synthetic ligands for peroxisome proliferator-activated receptor gamma (PPAR-gamma) represent an interesting tool for pharmacological interventions to treat inflammatory conditions. In particular, PPAR-gamma activation prevents pain and inflammation in the temporomandibular joint (TMJ) by decreasing cytokine release and stimulating the synthesis of endogenous opioids. The goal of this study was to clarify whether PPAR-gamma activation induces macrophage polarization, inhibiting inflammatory cytokine release and leukocyte recruitment. In addition, we investigated the involvement of heme oxygenase 1 (HO-1) in downstream events after PPAR-gamma activation. Our results demonstrate that PPAR-gamma activation ablates cytokine release by Bone Marrow-Derived Macrophages (BMDM) in vitro. 15d-PGJ(2) induces the PPAR-gamma heterodimer activation from rat macrophages, with macrophage polarization from M1-like cells toward M2-like cells. This response is mediated through HO-1. PPAR-gamma activation diminished neutrophil migration induced by carrageenan, which was also HO-1 dependent. Ca2+/calmodulin expression did not change after PPAR-gamma activation indicating that is not required for the activation of the intracellular L-arginine/NO/cGMP/K+ATP channel pathway. In summary, the anti-inflammatory actions induced by PPAR-gamma activation involve macrophage polarization. HO-1 expression is increased and HO-1 activity is required for the suppression of neutrophil migration.