Cargando…
Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis
BACKGROUND: Spermidine is a dietary polyamine that is able to activate protein tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a negative regulator of interferon-gamma (IFN-γ)-induced responses, and IFN-γ stimulation of immune cells is a critical process in the immunopathol...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767590/ https://www.ncbi.nlm.nih.gov/pubmed/24040033 http://dx.doi.org/10.1371/journal.pone.0073703 |
_version_ | 1782283667582746624 |
---|---|
author | Morón, Belén Spalinger, Marianne Kasper, Stephanie Atrott, Kirstin Frey-Wagner, Isabelle Fried, Michael McCole, Declan F. Rogler, Gerhard Scharl, Michael |
author_facet | Morón, Belén Spalinger, Marianne Kasper, Stephanie Atrott, Kirstin Frey-Wagner, Isabelle Fried, Michael McCole, Declan F. Rogler, Gerhard Scharl, Michael |
author_sort | Morón, Belén |
collection | PubMed |
description | BACKGROUND: Spermidine is a dietary polyamine that is able to activate protein tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a negative regulator of interferon-gamma (IFN-γ)-induced responses, and IFN-γ stimulation of immune cells is a critical process in the immunopathology of inflammatory bowel disease (IBD), we wished to explore the potential of spermidine for reducing pro-inflammatory effects in vitro and in vivo. METHODS: Human THP-1 monocytes were treated with IFN-γ and/or spermidine. Protein expression and phosphorylation were analyzed by Western blot, cytokine expression by quantitative-PCR, and cytokine secretion by ELISA. Colitis was induced in mice by dextran sodium sulfate (DSS) administration. Disease severity was assessed by recording body weight, colonoscopy and histology. RESULTS: Spermidine increased expression and activity of PTPN2 in THP-1 monocytes and reduced IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 and 3, as well as p38 mitogen-activated protein kinase (MAPK) in a PTPN2 dependent manner. Subsequently, IFN-γ-induced expression/secretion of intracellular cell adhesion molecule (ICAM)-1 mRNA, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 was reduced in spermidine-treated cells. The latter effects were absent in PTPN2-knockdown cells. In mice with DSS-induced colitis, spermidine treatment resulted in ameliorated weight loss and decreased mucosal damage indicating reduced disease severity. CONCLUSIONS: Activation of PTPN2 by spermidine ameliorates IFN-γ-induced inflammatory responses in THP-1 cells. Furthermore, spermidine treatment significantly reduces disease severity in mice with DSS-induced colitis; hence, spermidine supplementation and subsequent PTPN2 activation may be helpful in the treatment of chronic intestinal inflammation such as IBD. |
format | Online Article Text |
id | pubmed-3767590 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37675902013-09-13 Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis Morón, Belén Spalinger, Marianne Kasper, Stephanie Atrott, Kirstin Frey-Wagner, Isabelle Fried, Michael McCole, Declan F. Rogler, Gerhard Scharl, Michael PLoS One Research Article BACKGROUND: Spermidine is a dietary polyamine that is able to activate protein tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a negative regulator of interferon-gamma (IFN-γ)-induced responses, and IFN-γ stimulation of immune cells is a critical process in the immunopathology of inflammatory bowel disease (IBD), we wished to explore the potential of spermidine for reducing pro-inflammatory effects in vitro and in vivo. METHODS: Human THP-1 monocytes were treated with IFN-γ and/or spermidine. Protein expression and phosphorylation were analyzed by Western blot, cytokine expression by quantitative-PCR, and cytokine secretion by ELISA. Colitis was induced in mice by dextran sodium sulfate (DSS) administration. Disease severity was assessed by recording body weight, colonoscopy and histology. RESULTS: Spermidine increased expression and activity of PTPN2 in THP-1 monocytes and reduced IFN-γ-induced phosphorylation of signal transducer and activator of transcription (STAT) 1 and 3, as well as p38 mitogen-activated protein kinase (MAPK) in a PTPN2 dependent manner. Subsequently, IFN-γ-induced expression/secretion of intracellular cell adhesion molecule (ICAM)-1 mRNA, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 was reduced in spermidine-treated cells. The latter effects were absent in PTPN2-knockdown cells. In mice with DSS-induced colitis, spermidine treatment resulted in ameliorated weight loss and decreased mucosal damage indicating reduced disease severity. CONCLUSIONS: Activation of PTPN2 by spermidine ameliorates IFN-γ-induced inflammatory responses in THP-1 cells. Furthermore, spermidine treatment significantly reduces disease severity in mice with DSS-induced colitis; hence, spermidine supplementation and subsequent PTPN2 activation may be helpful in the treatment of chronic intestinal inflammation such as IBD. Public Library of Science 2013-09-09 /pmc/articles/PMC3767590/ /pubmed/24040033 http://dx.doi.org/10.1371/journal.pone.0073703 Text en © 2013 Morón 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 Morón, Belén Spalinger, Marianne Kasper, Stephanie Atrott, Kirstin Frey-Wagner, Isabelle Fried, Michael McCole, Declan F. Rogler, Gerhard Scharl, Michael Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title | Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title_full | Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title_fullStr | Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title_full_unstemmed | Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title_short | Activation of Protein Tyrosine Phosphatase Non-Receptor Type 2 by Spermidine Exerts Anti-Inflammatory Effects in Human THP-1 Monocytes and in a Mouse Model of Acute Colitis |
title_sort | activation of protein tyrosine phosphatase non-receptor type 2 by spermidine exerts anti-inflammatory effects in human thp-1 monocytes and in a mouse model of acute colitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767590/ https://www.ncbi.nlm.nih.gov/pubmed/24040033 http://dx.doi.org/10.1371/journal.pone.0073703 |
work_keys_str_mv | AT moronbelen activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT spalingermarianne activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT kasperstephanie activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT atrottkirstin activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT freywagnerisabelle activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT friedmichael activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT mccoledeclanf activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT roglergerhard activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis AT scharlmichael activationofproteintyrosinephosphatasenonreceptortype2byspermidineexertsantiinflammatoryeffectsinhumanthp1monocytesandinamousemodelofacutecolitis |