ISSN: 1838-7640Theranostics
Global reach, higher impact
Theranostics 2020; 10(24):11013-11025. doi:10.7150/thno.47516 This issue Cite
Research Paper
Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice
1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, RP China.
2. Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, RP China.
*These authors contributed equally to this study.
Citation:
Ma ZG, Kong CY, Wu HM, Song P, Zhang X, Yuan YP, Deng W, Tang QZ. Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice. Theranostics 2020; 10(24):11013-11025. doi:10.7150/thno.47516. https://www.thno.org/v10p11013.htm
Other stylesAbstract
Rationale: Clinical application of doxorubicin (DOX) is limited by its toxic cardiovascular side effects. Our previous study found that toll-like receptor (TLR) 5 deficiency attenuated cardiac fibrosis in mice. However, the role of TLR5 in DOX-induced cardiotoxicity remains unclear.
Methods: To further investigate this, TLR5-deficient mice were subjected to a single intraperitoneal injection of DOX to mimic an acute model.
Results: Here, we reported that TLR5 expression was markedly increased in response to DOX injection. Moreover, TLR5 deficiency exerted potent protective effects against DOX-related cardiac injury, whereas activation of TLR5 by flagellin exacerbated DOX injection-induced cardiotoxicity. Mechanistically, the effects of TLR5 were largely attributed to direct interaction with spleen tyrosine kinase to activate NADPH oxidase (NOX) 2, increasing the production of superoxide and subsequent activation of p38. The toxic effects of TLR5 activation in DOX-related acute cardiac injury were abolished by NOX2 deficiency in mice. Our further study showed that neutralizing antibody-mediated TLR5 depletion also attenuated DOX-induced acute cardiotoxicity.
Conclusion: These findings suggest that TLR5 deficiency attenuates DOX-induced cardiotoxicity in mice, and targeting TLR5 may provide feasible therapies for DOX-induced acute cardiotoxicity.
Keywords: Apoptosis, cardiotoxicity, doxorubicin, NOX2, TLR5
Citation styles
APA
Ma, Z.G., Kong, C.Y., Wu, H.M., Song, P., Zhang, X., Yuan, Y.P., Deng, W., Tang, Q.Z. (2020). Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice. Theranostics, 10(24), 11013-11025. https://doi.org/10.7150/thno.47516.
ACS
Ma, Z.G.; Kong, C.Y.; Wu, H.M.; Song, P.; Zhang, X.; Yuan, Y.P.; Deng, W.; Tang, Q.Z. Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice. Theranostics 2020, 10 (24), 11013-11025. DOI: 10.7150/thno.47516.
NLM
Ma ZG, Kong CY, Wu HM, Song P, Zhang X, Yuan YP, Deng W, Tang QZ. Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice. Theranostics 2020; 10(24):11013-11025. doi:10.7150/thno.47516. https://www.thno.org/v10p11013.htm
CSE
Ma ZG, Kong CY, Wu HM, Song P, Zhang X, Yuan YP, Deng W, Tang QZ. 2020. Toll-like receptor 5 deficiency diminishes doxorubicin-induced acute cardiotoxicity in mice. Theranostics. 10(24):11013-11025.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.