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Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation

BACKGROUND: We have already reported that TNF-α increases cardiomyocyte apoptosis and IL-10 treatment prevented these effects of TNF-α. Present study investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF-α induced cardiomyocyte apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Ca...

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Autores principales: Dhingra, Sanjiv, Bagchi, Ashim K., Ludke, Ana L., Sharma, Anita K., Singal, Pawan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176791/
https://www.ncbi.nlm.nih.gov/pubmed/21949832
http://dx.doi.org/10.1371/journal.pone.0025009
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author Dhingra, Sanjiv
Bagchi, Ashim K.
Ludke, Ana L.
Sharma, Anita K.
Singal, Pawan K.
author_facet Dhingra, Sanjiv
Bagchi, Ashim K.
Ludke, Ana L.
Sharma, Anita K.
Singal, Pawan K.
author_sort Dhingra, Sanjiv
collection PubMed
description BACKGROUND: We have already reported that TNF-α increases cardiomyocyte apoptosis and IL-10 treatment prevented these effects of TNF-α. Present study investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF-α induced cardiomyocyte apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Cardiomyocytes isolated from adult Sprague Dawley rats were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml) and TNF-α+IL-10 (ratio 1) for 4 h. Exposure to TNF-α resulted in an increase in cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay. IL-10 by itself had no effect, but it prevented TNF-α induced apoptosis. IL-10 treatment increased Akt levels within cardiomyocytes and this change was associated with an increase in Jak1 and Stat3 phosphorylation. Pre-exposure of cells to Akt inhibitor prevented IL-10 induced Stat3 phosphorylation. Furthermore, in the presence of Akt or Stat3 inhibitor, IL-10 treatment was unable to block TNF-α induced cardiomyocyte apoptosis. CONCLUSION: It is suggested that IL-10 modulation of TNF-α induced cardiomyocyte apoptosis is mediated by Akt via Stat3 activation.
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spelling pubmed-31767912011-09-26 Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation Dhingra, Sanjiv Bagchi, Ashim K. Ludke, Ana L. Sharma, Anita K. Singal, Pawan K. PLoS One Research Article BACKGROUND: We have already reported that TNF-α increases cardiomyocyte apoptosis and IL-10 treatment prevented these effects of TNF-α. Present study investigates the role of Akt and Jak/Stat pathway in the IL-10 modulation of TNF-α induced cardiomyocyte apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Cardiomyocytes isolated from adult Sprague Dawley rats were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml) and TNF-α+IL-10 (ratio 1) for 4 h. Exposure to TNF-α resulted in an increase in cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay. IL-10 by itself had no effect, but it prevented TNF-α induced apoptosis. IL-10 treatment increased Akt levels within cardiomyocytes and this change was associated with an increase in Jak1 and Stat3 phosphorylation. Pre-exposure of cells to Akt inhibitor prevented IL-10 induced Stat3 phosphorylation. Furthermore, in the presence of Akt or Stat3 inhibitor, IL-10 treatment was unable to block TNF-α induced cardiomyocyte apoptosis. CONCLUSION: It is suggested that IL-10 modulation of TNF-α induced cardiomyocyte apoptosis is mediated by Akt via Stat3 activation. Public Library of Science 2011-09-20 /pmc/articles/PMC3176791/ /pubmed/21949832 http://dx.doi.org/10.1371/journal.pone.0025009 Text en Dhingra et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dhingra, Sanjiv
Bagchi, Ashim K.
Ludke, Ana L.
Sharma, Anita K.
Singal, Pawan K.
Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title_full Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title_fullStr Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title_full_unstemmed Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title_short Akt Regulates IL-10 Mediated Suppression of TNFα-Induced Cardiomyocyte Apoptosis by Upregulating Stat3 Phosphorylation
title_sort akt regulates il-10 mediated suppression of tnfα-induced cardiomyocyte apoptosis by upregulating stat3 phosphorylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176791/
https://www.ncbi.nlm.nih.gov/pubmed/21949832
http://dx.doi.org/10.1371/journal.pone.0025009
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