title: Interleukin-1 signaling mediates acute doxorubicin-induced cardiotoxicity.
abstract: Doxorubicin (DOX) is a potent anticancer drug, which is widely used in the treatments of a variety of solid and hematopoietic tumours, but its use is limited by its cardiotoxicity and dose-dependent congestive heart failure. After we found the high expression of interleukin-1 receptor I (IL-1RI) gene in mice cardiac tissues with DOX-induced cardiotoxicity, we assumed interleukin-1 (IL-1) signaling might mediate acute DOX-induced cardiotoxicity. In this report, Balb/c mice were intraperitoneally injected with different dosage of DOX followed by different days of study. We found both IL-1β and interleukin-1 receptor antagonist (IL-1Ra) concentrations in serum were highly induced after DOX treatment, associated with increased IL-1RI expression in cardiac tissues. Furthermore, IL-1 signaling was found to express higher with the increased dosage of DOX treatment. Histology score of cardiac tissues showed obvious cardiac damage after DOX treatment, while assessment with the Spearman rank correlation coefficient showed that histology score was closely correlated with IL-1β and IL-1Ra concentrations in serum and IL-1RI expression in cardiac tissue. Our results reveal a potential role of IL-1 signaling in acute DOX-induced cardiotoxic injury and lead to an assumption that this signal system might be a potential candidate agent that inhibits cardiomyocyte-toxicity in DOX-exposed patients.
authors: Department of Cardiology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Jinzhou
authors: J
authors: Zhu
authors: Jing
authors: J
authors: Zhang
authors: Lin
authors: L
authors: Zhang
authors: Run
authors: R
authors: Du
authors: Di
authors: D
authors: Xiang
authors: Mingyuan
authors: M
authors: Wu
authors: Ruiyan
authors: R
authors: Zhang
authors: Wei
authors: W
authors: Han
mesh_terms: D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology; D007375:Interleukin-1 / Q000502:physiology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
chemical_list: C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D004317:Doxorubicin