炎癥是機體對內(nèi)外環(huán)境有害刺激產(chǎn)生的以防御為主的基本病理過程，但過強以及持續(xù)時間過長的炎癥均可導致非特異性組織損傷，因此炎癥反應的強度和時間在機體需受到嚴密調(diào)控。炎癥消退（inflammation resolution）是炎癥反應主動誘導的，多機制和多分子參與炎癥生理階段，是炎癥自身反饋性調(diào)控機制，起著終止炎癥反應作用，是炎癥自限的主要原因；其功能不足導致炎癥慢性化，與多種慢性炎癥性疾病密切相關(guān)；促炎癥消退分子抗炎機制不同于傳統(tǒng)藥物，為抗炎藥物研制新方向，因此發(fā)現(xiàn)新促炎癥消退分子并闡明其機理具重要意義。巨噬細胞吞噬凋亡細胞誘導的炎癥抑制和組織修復是促炎癥消退的核心機制，張志仁教授課題組前期研究發(fā)現(xiàn)了促紅細胞生成素（EPO）在生理條件下促巨噬細胞吞噬清除凋亡細胞作用（Immunity 2016, 44, 287–302）。在此基礎(chǔ)上，張志仁教授等發(fā)現(xiàn)炎癥條件下，浸潤吞噬細胞氧呼吸爆發(fā)可導致局部低氧而誘導局部EPO和巨噬細胞EPOR升高；進一步采用Lyz2-Cre-Eporloxp/loxp 小鼠，他們發(fā)現(xiàn)巨噬細胞EPOR通路在促進炎癥消退中起著重要作用，其機制與促進凋亡細胞吞噬清除及促進巨噬細胞淋巴結(jié)回流相關(guān)；并且EPO治療可顯著促進慢性炎癥的消退。
        該研究揭示了一條新的炎癥反饋調(diào)控通路，即“氧呼吸爆發(fā)-低氧-巨噬細胞EPOR通路激活-炎癥消退”；發(fā)現(xiàn)EPO為促炎癥消退新分子，為調(diào)控炎癥消退提供了新靶點，為臨床上炎癥相關(guān)疾病的治療提供了新靶點。

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An essential role of erythropoietin in promoting inflammation resolution discovered by Zhiren Zhang ａnd Yuzhang Wu Groups

Prof. Zhiren Zhang, Yuzhang Wu ａnd colleagues, Institute of Immunology，PLA, Third Military Medical University, have reported that macrophage erythropoeitin signaling is important for promoting inflammation resolution. This report entitled “Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution” was published on Nat. Commun. 7:12177 doi: 10.1038/ncomms12177 (2016).

Acute inflammation is a physiological response to tissue damage or infection that is self-limited ａnd generally beneficial to the host; however, ungoverned inflammation is highly detrimental ａnd is a unifying basis of many widely occurring diseases, such as atherosclerosis,obesity ａnd cancer. Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental ａnd of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia ａnd macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice ａnd chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, ａnd exogenous erythropoietin enhances this resolution in WT ａnd CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris ａnd enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions.

Article：Luo B, Wang J, Liu Z, Shen Z, Shi R, Liu YQ, Liu Y, Jiang M, Wu Y*, Zhang Z*. Phagocyte respiratory burst activates macrophage eryth

 本文由專注于提供生物科技服務的齊一生物收集整理