Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion
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Stefania De Santis1,2,*, Dale Kunde3,*, Grazia Serino1, Vanessa Galleggiante1,4, Maria Lucia Caruso5, Mauro Mastronardi6, Elisabetta Cavalcanti5, Nicole Ranson3, Aldo Pinto4, Pietro Campiglia4,7, Angelo Santino2, Rajaraman Eri3,*, Marcello Chieppa1,3,4,7,*
1IRCCS “de Bellis”, Laboratory of Experimental Immunopathology, Castellana Grotte (BA), Italy
2Institute of Sciences of Food Production, C.N.R. Unit of Lecce, Lecce, Italy
3Mucosal Biology, School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia
4Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy
5IRCCS “de Bellis”, Department of Pathology, Castellana Grotte (BA), Italy
6IRCCS “de Bellis”, Department of Gastroenterology, Castellana Grotte (BA), Italy
7European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
*These authors have contributed equally to this work
Marcello Chieppa, email: [email protected]
Keywords: polyphenols, dendritic cells, inflammation, SLPI, nutrition
Received: August 02, 2016 Accepted: September 21, 2016 Published: October 03, 2016
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.
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