title: Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion.
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 (TNFβ) 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.
authors.affiliation: IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte (BA), Italy.|Institute of Sciences of Food Production, C.N.R. Unit of Lecce, Lecce, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: De Santis
authors.affiliation: Mucosal Biology, School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.
authors.forename: Dale
authors.initials: D
authors.lastname: Kunde
authors.affiliation: IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte (BA), Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Serino
authors.affiliation: IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte (BA), Italy.|Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Galleggiante
authors.affiliation: IRCCS "de Bellis", Department of Pathology, Castellana Grotte (BA), Italy.
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Caruso
authors.affiliation: IRCCS "de Bellis", Department of Gastroenterology, Castellana Grotte (BA), Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Mastronardi
authors.affiliation: IRCCS "de Bellis", Department of Pathology, Castellana Grotte (BA), Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cavalcanti
authors.affiliation: Mucosal Biology, School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Ranson
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy.|European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.affiliation: Institute of Sciences of Food Production, C.N.R. Unit of Lecce, Lecce, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Santino
authors.affiliation: Mucosal Biology, School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.
authors.forename: Rajaraman
authors.initials: R
authors.lastname: Eri
authors.affiliation: IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte (BA), Italy.|Mucosal Biology, School of Human Life Sciences, University of Tasmania, Launceston, TAS, Australia.|Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), Italy.|European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Chieppa
mesh_terms: D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D053481:Secretory Leukocyte Peptidase Inhibitor; D014409:Tumor Necrosis Factor-alpha; D011794:Quercetin
keywords: SLPI; dendritic cells; inflammation; nutrition; polyphenols