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* Department of Human Morphology and
Institute of Pathology, Università degli Studi di Milano, Milan, Italy; and
Molecular Targeting Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy
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 
-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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was partially supported by Associazione Italiana per la Ricerca sul Cancro, Ricerca Finalizzata 2002, First 2004.
2 M.P. and A.B. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Cristiano Rumio, University of Milan, Department of Human Morphology, Via Mangiagalli 31, Milan, Italy. E-mail address: cristiano.rumio{at}unimi.it
4 Abbreviations used in this paper: EECC, enteroendocrine cell; ODN, oligodeoxynucleotide; Fw, forward; Rw, reverse; TRITC, tetramethylrhodamine isothiocyanate; DAPI, 4',6'-diamidino-2-phenylindole; KC, keratinocyte-derived chemokine; CCK, cholecystokinin; EIA, enzyme immunoassay; siRNA, small interfering RNA; PKC, protein kinase C.
This article has been cited by other articles:
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  S. Selleri, M. Palazzo, S. Deola, E. Wang, A. Balsari, F. M. Marincola, and C. Rumio Induction of pro-inflammatory programs in enteroendocrine cells by the Toll-like receptor agonists flagellin and bacterial LPS Int. Immunol., August 1, 2008; 20(8): 961 - 970. [Abstract] [Full Text] [PDF]
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