Cell Biology International

Previous studies have demonstrated that interleukins (ILs) are closely associated with doxorubicin (DOX)‐induced cardiac injury. IL‐5 is an important member of the IL family, and this study was performed to investigate whether IL‐5 affects DOX‐induced cardiac injury and its underlying mechanisms. The cardiac IL‐5 expression was first detected and the results showed that cardiac IL‐5 levels were significantly lower in DOX‐treated mice, and IL‐5 was mainly derived from cardiac macrophage (Mø). In addition, some DOX‐treated mice received an injection of anti‐IL‐5‐neutralizing antibody (nAb), and we found that treatment with a mouse anti‐IL‐5 nAb significantly upregulated the levels of myocardial injury markers, aggravated cardiac dysfunction, increased M1 macrophage (Mø1) and decreased M2 macrophage (Mø2) differentiation, and promoted apoptotic marker expression. Furthermore, the effect of mouse IL‐5 nAb on DOX‐induced Mø differentiation and its role on mouse cardiomyocyte (MCM) cells apoptosis were detected in vitro, and the results exhibited that mouse IL‐5 nAb promoted Mø1 differentiation but inhibited Mø2 differentiation in vitro and alleviated apoptosis in MCM cells. Our results found a mouse anti‐IL‐5 nAb‐aggravated DOX‐induced cardiac injury and dysfunction by alleviating the inflammatory response and myocardial cell apoptosis.

[1]  Jianfang Liu,et al.  Interleukin-12p35 knockout promotes macrophage differentiation, aggravates vascular dysfunction, and elevates blood pressure in angiotensin II-infused mice , 2018, Cardiovascular research.

[2]  Jianfang Liu,et al.  Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice , 2018, EBioMedicine.

[3]  Aaron R Navratil,et al.  Macrophage-Associated Lipin-1 Enzymatic Activity Contributes to Modified Low-Density Lipoprotein–Induced Proinflammatory Signaling and Atherosclerosis , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[4]  David M. Jones,et al.  Therapeutic effect of anti-IL-5 on eosinophilic myocarditis with large pericardial effusion , 2017, BMJ Case Reports.

[5]  Yung-Hyun Choi,et al.  HSP70-1 is required for interleukin-5-induced angiogenic responses through eNOS pathway , 2017, Scientific Reports.

[6]  R. Virmani,et al.  Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus. , 2017, Arteriosclerosis, thrombosis, and vascular biology.

[7]  S. Humphries,et al.  Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease , 2016, Cytokine.

[8]  S. Friedman,et al.  Granulocyte macrophage colony-stimulating factor is required for aortic dissection/intramural haematoma , 2015, Nature Communications.

[9]  W. Zhao,et al.  Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice , 2015, Gene Therapy.

[10]  Yujie Zhou,et al.  Valsartan Attenuates Atherosclerosis via Upregulating the Th2 Immune Response in Prolonged Angiotensin II-Treated ApoE−/− Mice , 2015, Molecular medicine.

[11]  S. Ryter,et al.  The Impact of Autophagy on Cell Death Modalities , 2014, International journal of cell biology.

[12]  H. Crijns,et al.  Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. , 2012, Journal of molecular and cellular cardiology.

[13]  K. Lim,et al.  Why is autophagy important in human diseases? , 2012, Experimental & Molecular Medicine.

[14]  K. Takatsu.  Interleukin-5 and IL-5 receptor in health and diseases , 2011, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[15]  F. Crea,et al.  Increase of plasma IL-9 and decrease of plasma IL-5, IL-7, and IFN-γ in patients with chronic heart failure , 2011, Journal of Translational Medicine.

[16]  Li-li Yin,et al.  OX-LDL up-regulates the vascular endothelial growth factor-to-pigment epithelium-derived factor ratio in human retinal pigment epithelial cells. , 2011, Current eye research.

[17]  Z. Qian,et al.  Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. , 2001, Life sciences.

[18]  W. Sewell,et al.  Induction of Interleukin-4 and Interleukin-5 Expression in Mast Cells Is Inhibited by Glucocorticoids , 1998, Clinical Diagnostic Laboratory Immunology.

[19]  K. Takatsu,et al.  Critical proline residues of the cytoplasmic domain of the IL-5 receptor alpha chain and its function in IL-5-mediated activation of JAK kinase and STAT5. , 1996, International immunology.

[20]  R. Egan,et al.  Effects of an antibody to interleukin-5 in a monkey model of asthma. , 1995, American journal of respiratory and critical care medicine.

[21]  K. Takatsu,et al.  A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction , 1994, Molecular and cellular biology.

[22]  D. Riches,et al.  Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF alpha) by interferons. Implications for the pleiotropic activities of TNF alpha. , 1994, The Journal of clinical investigation.

[23]  K. Takatsu,et al.  CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea. , 1992, The American review of respiratory disease.

[24]  Q. Tang,et al.  CTRP3 protected against doxorubicin-induced cardiac dysfunction, inflammation and cell death via activation of Sirt1. , 2018, Journal of molecular and cellular cardiology.

[25]  K. Takatsu,et al.  JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor alpha and betac subunit, respectively, and are activated upon IL-5 stimulation. , 1998, Blood.