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Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages
- Source :
- Mediators of Inflammation, Vol 2014 (2014), Mediators of Inflammation, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2014
- Publisher :
- Hindawi Publishing Corporation, 2014.
-
Abstract
- 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 IκBαdegradation 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.
- Subjects :
- Lipopolysaccharides
Male
medicine.medical_specialty
Article Subject
Immunology
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Nitric Oxide
digestive system
Nitric oxide
chemistry.chemical_compound
Internal medicine
ÓXIDO NÍTRICO
medicine
lcsh:Pathology
Animals
Rats, Wistar
Receptor
Protein kinase A
Cholecystokinin
biology
digestive, oral, and skin physiology
NF-kappa B
Cell Biology
Rats
Nitric oxide synthase
IκBα
Endocrinology
chemistry
Gastrointestinal hormone
Macrophages, Peritoneal
biology.protein
Signal transduction
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Research Article
lcsh:RB1-214
Subjects
Details
- Language :
- English
- ISSN :
- 09629351
- Database :
- OpenAIRE
- Journal :
- Mediators of Inflammation
- Accession number :
- edsair.doi.dedup.....85e02b408a2d9abea91707036e0e60fa
- Full Text :
- https://doi.org/10.1155/2014/896029