An essential role of erythropoietin in promoting inflammation resolution discovered by Zhiren Zhang and Yuzhang Wu Groups
Source：Yuzhang Wu
2016-07-26
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 erythropoietin signalling to promote acute inflammation resolution. 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 erythropoietin signalling to promote acute inflammation resolution. Nat. Commun. 7:12177 doi: 10.1038/ncomms12177 (2016).
