Cargando…
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...
Autores principales: | , , , , |
---|---|
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 |
_version_ | 1782212251755741184 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3176791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dhingrasanjiv aktregulatesil10mediatedsuppressionoftnfainducedcardiomyocyteapoptosisbyupregulatingstat3phosphorylation AT bagchiashimk aktregulatesil10mediatedsuppressionoftnfainducedcardiomyocyteapoptosisbyupregulatingstat3phosphorylation AT ludkeanal aktregulatesil10mediatedsuppressionoftnfainducedcardiomyocyteapoptosisbyupregulatingstat3phosphorylation AT sharmaanitak aktregulatesil10mediatedsuppressionoftnfainducedcardiomyocyteapoptosisbyupregulatingstat3phosphorylation AT singalpawank aktregulatesil10mediatedsuppressionoftnfainducedcardiomyocyteapoptosisbyupregulatingstat3phosphorylation |