title: Activation of enteroendocrine cells via TLRs induces hormone, chemokine, and defensin secretion.
abstract: Enteroendocrine cells are known primarily for their production of hormones that affect digestion, but they might also be implicated in sensing and neutralizing or expelling pathogens. We evaluate the expression of TLRs and the response to specific agonists in terms of cytokines, defensins, and hormones in enteroendocrine cells. The mouse enteroendocrine cell line STC-1 and C57BL/6 mice are used for in vitro and in vivo studies, respectively. The presence of TLR4, 5, and 9 is investigated by RT-PCR, Western blot, and immunofluorescence analyses. Activation of these receptors is studied evaluating keratinocyte-derived chemokine, defensins, and cholecystokinin production in response to their specific agonists. In this study, we show that the intestinal enteroendocrine cell line STC-1 expresses TLR4, 5, and 9 and releases cholecystokinin upon stimulation with the respective receptor agonists LPS, flagellin, and CpG-containing oligodeoxynucleotides. Release of keratinocyte-derived chemokine and beta-defensin 2 was also observed after stimulation of STC-1 cells with the three TLR agonists, but not with fatty acids. Consistent with these in vitro data, mice showed increased serum cholecystokinin levels after oral challenge with LPS, flagellin, or CpG oligodeoxynucleotides. In addition to their response to food stimuli, enteroendocrine cells sense the presence of bacterial Ags through TLRs and are involved in neutralizing intestinal bacteria by releasing chemokines and defensins, and maybe in removing them by releasing hormones such as cholecystokinin, which induces contraction of the muscular tunica, favoring the emptying of the distal small intestine.
authors: Department of Human Morphology, Institute of Pathology, Università degli Studi di Milano, Via Mangiagalli 31, Milan, Italy.
authors: Marco
authors: M
authors: Palazzo
authors: Andrea
authors: A
authors: Balsari
authors: Anna
authors: A
authors: Rossini
authors: Silvia
authors: S
authors: Selleri
authors: Claudia
authors: C
authors: Calcaterra
authors: Silvia
authors: S
authors: Gariboldi
authors: Laura
authors: L
authors: Zanobbio
authors: Francesca
authors: F
authors: Arnaboldi
authors: Yuri F
authors: YF
authors: Shirai
authors: Graziano
authors: G
authors: Serrao
authors: Cristiano
authors: C
authors: Rumio
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism*; D002766:Cholecystokinin / Q000097:blood / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000032:analysis / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C408982:CPG-oligonucleotide; D018925:Chemokines; C117047:Defb2 protein, mouse; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D034741:RNA, Small Interfering; D051193:Toll-Like Receptors; D023083:beta-Defensins; D005408:Flagellin; C074302:keratinocyte-derived chemokines; D002766:Cholecystokinin; D011493:Protein Kinase C