Cholecystokinin Inhibits Inducible Nitric Oxide Synthase Expression by Lipopolysaccharide-Stimulated Peritoneal Macrophages
| Autor: | Fabíola Mestriner, Rafael Simone Saia, Evelin Capellari Cárnio, Giuliana Bertozi, Fernando Q. Cunha |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
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 |
| Zdroj: | 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 |
| ISSN: | 0962-9351 |
| DOI: | 10.1155/2014/896029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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