Crocin Suppresses LPS-Stimulated Expression of Inducible Nitric Oxide Synthase by Upregulation of Heme Oxygenase-1 via Calcium/Calmodulin-Dependent Protein Kinase 4
| Autor: | Ga-Young Park, Ji-Hee Kim, Soo Young Bang, Soo-Kyung Bae, Sun Young Park, YoungHee Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Article Subject Immunology Nitric Oxide Synthase Type II Nitric oxide Cell Line Crocin chemistry.chemical_compound Mice Downregulation and upregulation Calmodulin lcsh:Pathology Animals Protein kinase A Protein kinase B biology Cell Biology Molecular biology Carotenoids Nitric oxide synthase Heme oxygenase chemistry biology.protein Phosphorylation Calcium Calcium-Calmodulin-Dependent Protein Kinase Type 4 Heme Oxygenase-1 lcsh:RB1-214 Research Article |
| Zdroj: | Mediators of Inflammation Mediators of Inflammation, Vol 2014 (2014) |
| ISSN: | 0962-9351 |
| DOI: | 10.1155/2014/728709 |
| Popis: | Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1) which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS) expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca2+mobilization from intracellular pools and phosphorylation of Ca2+/calmodulin-dependent protein kinase 4 (CAMK4). CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca2+/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation. |
| Databáze: | OpenAIRE |
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