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

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-galactosy...

Descripción completa

Detalles Bibliográficos
Autores principales: Sada, Masashi, Matsushima, Shouji, Ikeda, Masataka, Ikeda, Soichiro, Okabe, Kosuke, Ishikita, Akihito, Tadokoro, Tomonori, Enzan, Nobuyuki, Yamamoto, Taishi, Miyamoto, Hiroko Deguchi, Tsutsui, Yoshitomo, Miyake, Ryo, Setoyama, Daiki, Kang, Dongchon, Ide, Tomomi, Tsutsui, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Original Research - Preclinical
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504401/
https://www.ncbi.nlm.nih.gov/pubmed/37719427
http://dx.doi.org/10.1016/j.jacbts.2023.02.014
Descripción
Sumario: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.

Ejemplares similares