Igarashi Hirotaka, Ohno Koichi, Fujiwara-Igarashi Aki, Kanemoto Hideyuki, Fukushima Kenjiro, Goto-Koshino Yuko, Uchida Kazuyuki, Tsujimoto Hajime
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.
J Vet Med Sci. 2015 Apr;77(4):439-47. doi: 10.1292/jvms.14-0505. Epub 2014 Dec 20.
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.
炎症性结肠息肉（ICRPs）在日本的迷你腊肠犬（MDs）中频繁出现。患有ICRPs的MDs会出现多个息肉，并伴有严重的中性粒细胞浸润，对免疫抑制治疗有反应。因此，ICRPs被认为是犬类炎症性肠病（IBD）的一种新的、特定品种形式。模式识别受体（PRRs）在区分病原体与共生细菌和食物抗原方面起关键作用。PRRs基因紊乱导致的功能障碍与人类和犬类IBD有关。因此，我们分析了患有ICRPs的MDs中PRRs的反应性。招募了26只患有ICRPs的MDs和16只对照MDs。从每只狗身上获取外周血来源的单核细胞，然后用PRR配体刺激6小时和24小时；随后，分别使用定量实时PCR和ELISA定量白细胞介素-1β（IL-1β）的信使核糖核酸（mRNA）表达水平和蛋白质分泌。用核苷酸结合寡聚化结构域2（NOD2）配体刺激后，受ICRP影响的MDs单核细胞中IL-1β mRNA水平和蛋白质分泌显著高于对照MDs。此外，Toll样受体（TLR）1/2、TLR2和TLR2/6刺激诱导的IL-1β蛋白质分泌在受ICRP影响的MDs中也显著更高。这些结果表明，受ICRP影响的MDs中对NOD2、TLR1/2、TLR2和TLR2/6信号的反应性增强，可能在MDs中ICRPs的发病机制中起作用。应对这些PRRs的遗传背景进行进一步研究。
