title: Expression and function of TLR2, TLR4, and Nod2 in primary canine colonic epithelial cells.
abstract: The gut maintains a delicate balance between the downregulation of inflammatory reactions to commensal bacteria and the capacity to respond to pathogens with vigorous cellular and humoral immune responses. Intestinal epithelial cells, including colonic epithelial cells (CECs) possess many properties of cells of the innate immune system, in particular the ability to recognize and respond to microbial antigens. Recognition of microorganisms by CECs is based upon their recognition of signature molecules, called microbe-associated molecular patterns (MAMP), by pattern recognition receptors (PRR) including membrane toll-like receptors (TLR) and cytosolic Nod2, an intracellular counterpart of TLRs. The purpose of this study was to determine whether primary CECs from normal dogs express a functional TLR2, TLR4, and Nod2 and whether they are regulated by inflammatory mediators. We show that canine primary CECs express TLR2, TLR4, and Nod2 that can be modulated in response to their respective MAMPs, lipopolysaccharides (LPS) or peptidoglycans (PGN). Furthermore, we demonstrate that these receptors are functional as evidenced by the induction of cytokine gene expression in response to LPS or PGN.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Swerdlow
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Kennedy
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Washabau
authors.forename: Paula S
authors.initials: PS
authors.lastname: Henthorn
authors.forename: Peter F
authors.initials: PF
authors.lastname: Moore
authors.forename: Simon R
authors.initials: SR
authors.lastname: Carding
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felsburg
mesh_terms: D000818:Animals; D003106:Colon / Q000166:cytology / Q000276:immunology*; D004285:Dogs / Q000276:immunology*; D004847:Epithelial Cells; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D010457:Peptidoglycan / Q000494:pharmacology; D010865:Pilot Projects; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D053473:Nod2 Signaling Adaptor Protein; D010457:Peptidoglycan; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D012313:RNA