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Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages
Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However, apart from its gastrointestinal effects, studies have described that CCK also plays immunoregulatory roles. Taking in account the involvement of inducible nitric oxide synthase- (iNOS-) derived NO in the sepsis context...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122025/ https://www.ncbi.nlm.nih.gov/pubmed/25125801 http://dx.doi.org/10.1155/2014/896029 |
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author | Saia, Rafael Simone Mestriner, Fabíola Leslie Bertozi, Giuliana Cunha, Fernando Queiróz Cárnio, Evelin Capellari |
author_facet | Saia, Rafael Simone Mestriner, Fabíola Leslie Bertozi, Giuliana Cunha, Fernando Queiróz Cárnio, Evelin Capellari |
author_sort | Saia, Rafael Simone |
collection | PubMed |
description | Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However, apart from its gastrointestinal effects, studies have described that CCK also plays immunoregulatory roles. Taking in account the involvement of inducible nitric oxide synthase- (iNOS-) derived NO in the sepsis context, the present study was undertaken to investigate the role of CCK on iNOS expression in LPS-activated peritoneal macrophages. Our results revealed that CCK reduces NO production and attenuates the iNOS mRNA expression and protein formation. Furthermore, CCK inhibited the nuclear factor- (NF-) κB pathway reducing IκBα degradation and minor p65-dependent translocation to the nucleus. Moreover, CCK restored the intracellular cAMP content activating the protein kinase A (PKA) pathway, which resulted in a negative modulatory role on iNOS expression. In peritoneal macrophages, the CCK-1R expression, but not CCK-2R, was predominant and upregulated by LPS. The pharmacological studies confirmed that CCK-1R subtype is the major receptor responsible for the biological effects of CCK. These data suggest an anti-inflammatory role for the peptide CCK in modulating iNOS-derived NO synthesis, possibly controlling the macrophage activation through NF-κB, cAMP-PKA, and CCK-1R pathways. Based on these findings, CCK could be used as an adjuvant agent to modulate the inflammatory response and prevent systemic complications commonly found during sepsis. |
format | Online Article Text |
id | pubmed-4122025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-41220252014-08-14 Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages Saia, Rafael Simone Mestriner, Fabíola Leslie Bertozi, Giuliana Cunha, Fernando Queiróz Cárnio, Evelin Capellari Mediators Inflamm Research Article Cholecystokinin (CCK) was first described as a gastrointestinal hormone. However, apart from its gastrointestinal effects, studies have described that CCK also plays immunoregulatory roles. Taking in account the involvement of inducible nitric oxide synthase- (iNOS-) derived NO in the sepsis context, the present study was undertaken to investigate the role of CCK on iNOS expression in LPS-activated peritoneal macrophages. Our results revealed that CCK reduces NO production and attenuates the iNOS mRNA expression and protein formation. Furthermore, CCK inhibited the nuclear factor- (NF-) κB pathway reducing IκBα degradation and minor p65-dependent translocation to the nucleus. Moreover, CCK restored the intracellular cAMP content activating the protein kinase A (PKA) pathway, which resulted in a negative modulatory role on iNOS expression. In peritoneal macrophages, the CCK-1R expression, but not CCK-2R, was predominant and upregulated by LPS. The pharmacological studies confirmed that CCK-1R subtype is the major receptor responsible for the biological effects of CCK. These data suggest an anti-inflammatory role for the peptide CCK in modulating iNOS-derived NO synthesis, possibly controlling the macrophage activation through NF-κB, cAMP-PKA, and CCK-1R pathways. Based on these findings, CCK could be used as an adjuvant agent to modulate the inflammatory response and prevent systemic complications commonly found during sepsis. Hindawi Publishing Corporation 2014 2014-07-13 /pmc/articles/PMC4122025/ /pubmed/25125801 http://dx.doi.org/10.1155/2014/896029 Text en Copyright © 2014 Rafael Simone Saia et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Saia, Rafael Simone Mestriner, Fabíola Leslie Bertozi, Giuliana Cunha, Fernando Queiróz Cárnio, Evelin Capellari Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title | Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title_full | Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title_fullStr | Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title_full_unstemmed | Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title_short | Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages |
title_sort | cholecystokinin inhibits inducible nitric oxide synthase expression by lipopolysaccharide-stimulated peritoneal macrophages |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122025/ https://www.ncbi.nlm.nih.gov/pubmed/25125801 http://dx.doi.org/10.1155/2014/896029 |
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