Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells

  • Authors:
    • Run-Min Guo
    • Wen-Ming Xu
    • Jian-Cong Lin
    • Li-Qiu Mo
    • Xiao-Xiao Hua
    • Pei-Xi Chen
    • Keng Wu
    • Dong-Dan Zheng
    • Jian-Qiang Feng
  • View Affiliations

  • Published online on: June 26, 2013     https://doi.org/10.3892/mmr.2013.1554
  • Pages: 603-608
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Abstract

A number of studies have demonstrated that inflammation plays a role in doxorubicin (DOX)-induced cardiotoxicity. However, the molecular mechanism by which DOX induces cardiac inflammation has yet to be fully elucidated. The present study aimed to investigate the role of the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway in DOX-induced inflammation and cytotoxicity. The results of our study demonstrated that the exposure of H9c2 cardiac cells to DOX reduced cell viability and stimulated an inflammatory response, as demonstrated by an increase in the levels of interleukin-1β (IL-1β) and IL-6, as well as tumor necrosis factor-α (TNF-α) production. Notably, DOX exposure induced the overexpression of phosphorylated p38 MAPK and phosphorylation of the NF-κB p65 subunit, which was markedly inhibited by SB203580, a specific inhibitor of p38 MAPK. The inhibition of NF-κB by pyrrolidine dithiocarbamate (PDTC), a selective inhibitor of NF-κB, significantly ameliorated DOX-induced inflammation, leading to a decrease in the levels of IL-1β and IL-6, as well as TNF-α production in H9c2 cells. The pretreatment of H9c2 cells with either SB203580 or PDTC before exposure to DOX significantly attenuated DOX-induced cytotoxicity. In conclusion, our study provides novel data demonstrating that the p38 MAPK/NF-κB pathway is important in the induction of DOX-induced inflammation and cytotoxicity in H9c2 cardiac myocytes.
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August 2013
Volume 8 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Guo, R., Xu, W., Lin, J., Mo, L., Hua, X., Chen, P. ... Feng, J. (2013). Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells. Molecular Medicine Reports, 8, 603-608. https://doi.org/10.3892/mmr.2013.1554
MLA
Guo, R., Xu, W., Lin, J., Mo, L., Hua, X., Chen, P., Wu, K., Zheng, D., Feng, J."Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells". Molecular Medicine Reports 8.2 (2013): 603-608.
Chicago
Guo, R., Xu, W., Lin, J., Mo, L., Hua, X., Chen, P., Wu, K., Zheng, D., Feng, J."Activation of the p38 MAPK/NF-κB pathway contributes to doxorubicin-induced inflammation and cytotoxicity in H9c2 cardiac cells". Molecular Medicine Reports 8, no. 2 (2013): 603-608. https://doi.org/10.3892/mmr.2013.1554