title: Transcriptional modulation of pattern recognition receptors in acute colitis in mice.
abstract: Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), contribute to the development of intestinal inflammatory diseases, like inflammatory bowel disease (IBD). Supporting investigations of the underlying mechanisms of IBD, this study provides an extensive PRR expression survey together with T-cell associated factors along the murine colon during experimental colitis. 8-12 week-old C57BL/6 mice were treated with dextran sodium sulfate (DSS) to induce colitis. The mRNA expression levels of Tlr1-9, Nod1, Nod2, T cell subset-associated master transcription factors and cytokines were determined using qPCR. The expression of TLR2, 4, 5 and 6 was determined with immunohistochemistry. Th1 and Th17 associated responses were quantified in the mesenteric lymph nodes (mLNs) using flow cytometry. In DSS treated mice, the mRNA expression of the majority of PRRs was increased relative to healthy controls and correlated with the degree of inflammation. The exceptions were Tlr1 and Tlr5, which displayed unchanged and down-regulated transcription, respectively. Furthermore, in healthy animals, there was increased transcription of Tlr2, 3 and 5 near the caecum as opposed the region near the rectum. Within the inflamed regions, the mRNA expression of Th1-, Th17- and regulatory T-cell associated cytokines was enhanced, while there was no change for Th2-associated cytokines. In agreement with the mRNA expression, enhanced IFNγ and IL-17 producing cells were observed in stimulated mLNs. This study provides an extensive expression survey of PRRs along the colon during the acute colitis and shows that the induced inflammation is characterized by a Th1- and IL-17 mediated cytokine response.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
authors.forename: Bin
authors.initials: B
authors.lastname: Zheng
authors.forename: Mary E
authors.initials: ME
authors.lastname: Morgan
authors.forename: Hendrik J G
authors.initials: HJ
authors.lastname: van de Kant
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051192:Receptors, Pattern Recognition / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D012333:RNA, Messenger; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors; D016264:Dextran Sulfate
keywords: Inflammatory bowel disease; NOD; TLR; Th1 cells; Th17 cells