IL-27p28 knockout aggravates Doxorubicin-induced cardiotoxicity by regulating Macrophage polarization

Abstract

BackgroundSeveral interleukins (ILs) have been demonstrated to participate in cardiac injury. This study aimed to investigate whether IL-27p28 plays a regulatory role in doxorubicin (DOX)-induced cardiac injury by regulating inflammation and oxidative stress. MethodsDox was used to establish a mouse cardiac injury model, and IL-27p28 was knocked out to observe its role in cardiac injury. In addition, monocytes were adoptively transferred to clarify whether monocyte-macrophages mediate the regulatory role of IL-27p28 in DOX-induced cardiac injury. ResultsIL-27p28 knockout significantly aggravated DOX-induced cardiac injury and cardiac dysfunction. IL-27p28 knockout also upregulated the phosphorylation levels of p65 and STAT1 and promoted M1 macrophage polarization in DOX-treated mice, which increased cardiac inflammation and oxidative stress. Moreover, IL-27p28-knockout mice that were adoptively transferred WT monocytes exhibited worse cardiac injury and cardiac dysfunction and higher cardiac inflammation and oxidative stress. ConclusionsIL-27p28 knockdown aggravates DOX-induced cardiac injury by worsening the M1 macrophage/M2 macrophage imbalance and its associated inflammatory response and oxidative stress.