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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...

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Autores principales: Saia, Rafael Simone, Mestriner, Fabíola Leslie, Bertozi, Giuliana, Cunha, Fernando Queiróz, Cárnio, Evelin Capellari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
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.
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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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