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Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion
Citation
De Santis, S and Kunde, D and Serino, G and Galleggiante, V and Caruso, ML and Mastronardi, M and Cavalcanti, E and Ranson, N and Pinto, A and Campiglia, P and Santino, A and Eri, R and Chieppa, M, Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion, Oncotarget, 7, (46) pp. 75800-75809. ISSN 1949-2553 (2016) [Refereed Article]
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Copyright Statement
Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0) https://creativecommons.org/licenses/by/3.0/
DOI: doi:10.18632/oncotarget.12415
Abstract
Dendritic cells (DCs) are professional antigen presenting cells (APCs) that in response to microbial infections generate long-lasting adaptive immune response. Following microbial uptake, DCs undergo a cascade of cellular differentiation that ultimately leads to "mature" DCs. Mature DCs produce a variety of inflammatory cytokines, including tumor necrosis factor-α (TNFα) a key cytokine for the inflammatory cascade. In numerous studies, polyphenols, including quercetin, demonstrated their ability to suppress TNFα secretion and protect from the onset of chronic inflammatory disorders. We show that murine bone marrow derived DCs express Slpi following quercetin exposure. Slpi is known to suppress LPS mediated NFκB activation, thus, it was hypothesized that its expression could be the key step for polyphenol induced inflammatory suppression. Slpi-KO DCs poorly respond to quercetin administration failing to reduce TNFα secretion in response to quercetin exposure. Supernatant from quercetin exposed DCs could also reduce LPS-mediated TNFα secretion by unrelated DCs, but this property is lost using an anti-Slpi antibody. In vivo, oral administration of quercetin is able to induce Slpi expression. Human biopsies from inflamed tract of the intestine reveal the presence of numerous SLPI+ cells and the expression level could be further increased by quercetin administration. We propose that quercetin induces Slpi expression that in turn reduces the inflammatory response. Our data encourages the development of nutritional strategies to improve the efficiency of current therapies for intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | SLPI, colitis, TNF, dendritic cells |
| Research Division: | Biological Sciences |
| Research Group: | Genetics |
| Research Field: | Genetic Immunology |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Digestive System Disorders |
| Author: | Kunde, D (Dr Dale Kunde) |
| Author: | Ranson, N (Mrs Nicole Ranson) |
| Author: | Eri, R (Associate Professor Raj Eri) |
| ID Code: | 111919 |
| Year Published: | 2016 |
| Web of Science® Times Cited: | 4 |
| Deposited By: | Health Sciences |
| Deposited On: | 2016-10-15 |
| Last Modified: | 2018-02-07 |
| Downloads: | 72 View Download Statistics |
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