PMID- 27716626
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181202
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 46
DP  - 2016 Nov 15
TI  - Secretory leukoprotease inhibitor is required for efficient quercetin-mediated 
      suppression of TNFalpha secretion.
PG  - 75800-75809
LID - 10.18632/oncotarget.12415 [doi]
AB  - 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-alpha (TNFbeta) a key cytokine 
      for the inflammatory cascade. In numerous studies, polyphenols, including 
      quercetin, demonstrated their ability to suppress TNFalpha 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 NFkappaB 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 TNFalpha secretion in 
      response to quercetin exposure. Supernatant from quercetin exposed DCs could also 
      reduce LPS-mediated TNFalpha 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.
FAU - De Santis, Stefania
AU  - De Santis S
AD  - IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte 
      (BA), Italy.
AD  - Institute of Sciences of Food Production, C.N.R. Unit of Lecce, Lecce, Italy.
FAU - Kunde, Dale
AU  - Kunde D
AD  - Mucosal Biology, School of Human Life Sciences, University of Tasmania, 
      Launceston, TAS, Australia.
FAU - Serino, Grazia
AU  - Serino G
AD  - IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte 
      (BA), Italy.
FAU - Galleggiante, Vanessa
AU  - Galleggiante V
AD  - IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte 
      (BA), Italy.
AD  - Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), 
      Italy.
FAU - Caruso, Maria Lucia
AU  - Caruso ML
AD  - IRCCS "de Bellis", Department of Pathology, Castellana Grotte (BA), Italy.
FAU - Mastronardi, Mauro
AU  - Mastronardi M
AD  - IRCCS "de Bellis", Department of Gastroenterology, Castellana Grotte (BA), Italy.
FAU - Cavalcanti, Elisabetta
AU  - Cavalcanti E
AD  - IRCCS "de Bellis", Department of Pathology, Castellana Grotte (BA), Italy.
FAU - Ranson, Nicole
AU  - Ranson N
AD  - Mucosal Biology, School of Human Life Sciences, University of Tasmania, 
      Launceston, TAS, Australia.
FAU - Pinto, Aldo
AU  - Pinto A
AD  - Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), 
      Italy.
FAU - Campiglia, Pietro
AU  - Campiglia P
AD  - Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), 
      Italy.
AD  - European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.
FAU - Santino, Angelo
AU  - Santino A
AD  - Institute of Sciences of Food Production, C.N.R. Unit of Lecce, Lecce, Italy.
FAU - Eri, Rajaraman
AU  - Eri R
AD  - Mucosal Biology, School of Human Life Sciences, University of Tasmania, 
      Launceston, TAS, Australia.
FAU - Chieppa, Marcello
AU  - Chieppa M
AD  - IRCCS "de Bellis", Laboratory of Experimental Immunopathology, Castellana Grotte 
      (BA), Italy.
AD  - Mucosal Biology, School of Human Life Sciences, University of Tasmania, 
      Launceston, TAS, Australia.
AD  - Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano (SA), 
      Italy.
AD  - European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Secretory Leukocyte Peptidase Inhibitor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Animals
MH  - Colon/drug effects/metabolism
MH  - Dendritic Cells/drug effects/immunology/metabolism
MH  - Extracellular Space/metabolism
MH  - Gene Expression
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice
MH  - Quercetin/*pharmacology
MH  - Secretory Leukocyte Peptidase Inhibitor/*genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC5342779
OTO - NOTNLM
OT  - SLPI
OT  - dendritic cells
OT  - inflammation
OT  - nutrition
OT  - polyphenols
COIS- CONFLICTS OF INTERESTS The authors declare no financial or commercial conflict of 
      interest.
EDAT- 2016/10/08 06:00
MHDA- 2018/02/27 06:00
PMCR- 2016/11/15
CRDT- 2016/10/08 06:00
PHST- 2016/08/02 00:00 [received]
PHST- 2016/09/21 00:00 [accepted]
PHST- 2016/10/08 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/10/08 06:00 [entrez]
PHST- 2016/11/15 00:00 [pmc-release]
AID - 12415 [pii]
AID - 10.18632/oncotarget.12415 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Nov 15;7(46):75800-75809. doi: 10.18632/oncotarget.12415.