Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion
Stefania De Santis, Dale Kunde, Grazia Serino, Vanessa Galleggiante, Maria Lucia Caruso, Mauro Mastronardi, Elisabetta Cavalcanti, Nicole Ranson, Aldo Pinto, Pietro Campiglia, Angelo Santino, Rajaraman Eri, Marcello Chieppa
Dendritic cells (DCs) are professional antigen presenting cells (APCs) that produce a variety of inflammatory cytokines following LPS exposure. These include tumor necrosis factor-a (TNFα) a key cytokine for the maintenance of chronic inflammation of the intestinal mucosa in IBD. 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 secretory leukocyte protease inhibitor (Slpi) following quercetin exposure. Slpi is known to suppress LPS mediated NFkB 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. 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.
- Chemokines & Homing