title: Functional analysis of pattern recognition receptors in miniature dachshunds with inflammatory colorectal polyps.
abstract: Inflammatory colorectal polyps (ICRPs) frequently occur in miniature dachshunds (MDs) in Japan. MDs with ICRPs develop multiple polyps with severe neutrophil infiltration that respond to immunosuppressive therapy. Therefore, ICRPs are thought to constitute a novel, breed-specific form of canine inflammatory bowel disease (IBD). Pattern recognition receptors (PRRs) play a key role in the distinction of pathogens from commensal bacteria and food antigens. Dysfunction resulting from genetic disorders of PRRs have been linked to human and canine IBD. Therefore, we analyzed the reactivity of PRRs in MDs with ICRPs. Twenty-six MDs with ICRPs and 16 control MDs were recruited. Peripheral blood-derived monocytes were obtained from each dog and then stimulated with PRR ligands for 6 and 24 hr; subsequently, messenger RNA (mRNA) expression levels and protein secretion of IL-1β were quantified using quantitative real-time PCR and ELISA, respectively. The levels of IL-1β mRNA and protein secretion after stimulation with a nucleotide-binding oligomerization domain 2 (NOD2) ligand were significantly greater in monocytes from ICRP-affected MDs than in those from control MDs. In addition, IL-1β protein secretion induced by toll-like receptor (TLR) 1/2, TLR2 and TLR2/6 stimulation was also significantly greater in ICRP-affected MDs. These results suggest that reactivity against NOD2, TLR1/2, TLR2 and TLR2/6 signals is enhanced in ICRP-affected MDs and may play a role in the pathogenesis of ICRPs in MDs. Additional studies of the genetic background of these PRRs should be performed.
authors: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors: Hirotaka
authors: H
authors: Igarashi
authors: Koichi
authors: K
authors: Ohno
authors: Aki
authors: A
authors: Fujiwara-Igarashi
authors: Hideyuki
authors: H
authors: Kanemoto
authors: Kenjiro
authors: K
authors: Fukushima
authors: Yuko
authors: Y
authors: Goto-Koshino
authors: Kazuyuki
authors: K
authors: Uchida
authors: Hajime
authors: H
authors: Tsujimoto
mesh_terms: D000818:Animals; D003111:Colonic Polyps / Q000378:metabolism / Q000662:veterinary*; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007249:Inflammation / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D051192:Receptors, Pattern Recognition
references: Tissue Antigens. 2011 Aug;78(2):94-101
references: 21623734
references: Vet Immunol Immunopathol. 2007 May 15;117(1-2):55-66
references: 17346803
references: Mem Inst Oswaldo Cruz. 2005 Aug;100(5):521-4
references: 16184230
references: World J Gastroenterol. 2010 Mar 7;16(9):1050-6
references: 20205273
references: J Clin Invest. 2008 Feb;118(2):545-59
references: 18188453
references: J Gastroenterol. 2009;44(8):803-11
references: 19547909
references: Tissue Antigens. 2010 Jul;76(1):48-56
references: 20403135
references: J Vet Med Sci. 2012 Jan;74(1):59-64
references: 21897060
references: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references: 12184808
references: Nat Immunol. 2004 Aug;5(8):800-8
references: 15220916
references: J Am Anim Hosp Assoc. 1997 Mar-Apr;33(2):156-60
references: 9111726
references: Clin Immunol. 2006 May;119(2):156-65
references: 16480927
references: Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1157-63
references: 16439468
references: Anim Health Res Rev. 2012 Jun;13(1):78-88
references: 22647637
references: PLoS One. 2010;5(12):e15740
references: 21203467
references: Autoimmun Rev. 2012 Nov;12(1):44-51
references: 22884558
references: Scand J Immunol. 2014 Aug;80(2):85-94
references: 24813376
references: Am J Physiol Gastrointest Liver Physiol. 2007 Mar;292(3):G767-78
references: 17138965
references: J Am Vet Med Assoc. 1979 Jan 1;174(1):72-5
references: 457574
references: Nature. 2012 Nov 1;491(7422):119-24
references: 23128233
references: J Biol Chem. 2001 Feb 16;276(7):4812-8
references: 11087742
references: Vet Immunol Immunopathol. 2009 Oct 15;131(3-4):298-302
references: 19446888
references: Nature. 2001 May 31;411(6837):603-6
references: 11385577
references: Vet Immunol Immunopathol. 2014 Sep 15;161(1-2):32-41
references: 25017709
references: Nature. 1997 Jul 24;388(6640):394-7
references: 9237759
references: Biotechnol Lett. 2004 Mar;26(6):509-15
references: 15127793
references: Mucosal Immunol. 2008 Nov;1 Suppl 1:S5-9
references: 19079230
references: Nat Immunol. 2011 Aug;12(8):709-14
references: 21772279
references: Vet Immunol Immunopathol. 2008 Aug 15;124(3-4):230-40
references: 18471895
references: J Immunol. 2004 Apr 15;172(8):4733-43
references: 15067049
references: Immunology. 2008 Apr;123(4):600-5
references: 18028374
references: Vet Immunol Immunopathol. 2012 Feb 15;145(3-4):618-24
references: 22321737
references: EMBO J. 2004 Apr 7;23(7):1587-97
references: 15044951
references: J Vet Med Sci. 2007 Sep;69(9):915-24
references: 17917376
references: Nature. 2007 Jul 26;448(7152):427-34
references: 17653185
references: Vet Immunol Immunopathol. 2013 Nov 15;156(1-2):32-42
references: 24148828
references: Nat Cell Biol. 2006 Dec;8(12):1327-36
references: 17128265
references: BMC Mol Biol. 2007;8:62
references: 17651481
references: Cancer Res. 2004 Aug 1;64(15):5245-50
references: 15289330
references: Vet Immunol Immunopathol. 2013 Oct 1;155(4):259-63
references: 23953369
references: Nat Genet. 2000 Jun;25(2):187-91
references: 10835634
references: Nature. 2006 Jul 6;442(7098):39-44
references: 16823444
references: Front Immunol. 2014 Feb 18;5:60
references: 24600450
references: Nat Rev Immunol. 2007 May;7(5):353-64
references: 17457343
references: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19440-5
references: 18032608
references: PLoS One. 2012;7(1):e30117
references: 22279566
references: Nat Rev Immunol. 2010 Feb;10(2):131-44
references: 20098461
references: J Vet Med Sci. 2011 Jun;73(6):773-8
references: 21304216
references: Inflamm Bowel Dis. 2010 Sep;16(9):1583-97
references: 20803699