IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death

Overview

Journal JACC Basic Transl Sci

Date 2023 Sep 18

PMID 37719427

Authors

Masashi Sada

Shouji Matsushima

Masataka Ikeda

Soichiro Ikeda

Kosuke Okabe

Akihito Ishikita

Tomonori Tadokoro

Nobuyuki Enzan

Taishi Yamamoto

Hiroko Deguchi Miyamoto

Yoshitomo Tsutsui

Ryo Miyake

Daiki Setoyama

Dongchon Kang

Tomomi Ide

Hiroyuki Tsutsui

Affiliations

Soon will be listed here.

Abstract

Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway.

Citing Articles

INKing the Cardiotoxicity Out of Doxorubicin.

Guo Z, Javaheri A JACC Basic Transl Sci. 2023; 8(8):1008-1009.

PMID: 37719425 PMC: 10504426. DOI: 10.1016/j.jacbts.2023.05.001.

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