Schmitz Silke, Werling Dirk, Allenspach Karin
Department of Veterinary Sciences and Services, Royal Veterinary College, University of London, Hawkshead Campus, North Mymms, United Kingdom.
Department of Pathology and Pathogen Biology, Royal Veterinary College, University of London, Hawkshead Campus, North Mymms, United Kingdom.
PLoS One. 2015 Mar 23;10(3):e0120779. doi: 10.1371/journal.pone.0120779. eCollection 2015.
Inflammasomes coordinate the maturation of IL-1β and IL-18 in response to danger signals. They are vital for maintenance of intestinal homeostasis and have been linked to chronic intestinal inflammation in humans. Probiotics have been advocated as treatment in intestinal inflammation. So far, no study has investigated the role of the inflammasome in canine chronic enteropathy (CE). In this study the intestinal expression of inflammasome components was assessed in CE dogs compared to controls, when treated with probiotic Enterococcus faecium (EF) ex-vivo and in-vivo. RNA extraction from endoscopic biopsies and reverse-transcriptase quantitative PCR was performed for NLRP3, casp-1, IL-1β and IL-18. Immunohistochemistry was performed to investigate protein expression in tissues. Gene expression of casp-1 and NLRP3 was lower in CE samples than controls. Ex-vivo treatment with EF reduced NLRP3 expression in control samples. Treatment of CE dogs with EF alongside dietary intervention had no effect on gene expression. In contrast, IL-1β protein expression in CE decreased with dietary treatment (but not with probiotics). The results of this study suggest that the inflammasome or its components may be partially involved in the inflammatory process seen in CE, but distinct from intestinal inflammation in humans.
炎性小体可响应危险信号来协调白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的成熟。它们对于维持肠道内稳态至关重要,并且与人类的慢性肠道炎症有关。益生菌已被提倡用于肠道炎症的治疗。到目前为止,尚无研究调查炎性小体在犬慢性肠病(CE)中的作用。在本研究中,将CE犬与对照犬相比,评估了炎性小体成分的肠道表达情况,这些犬在体外和体内用益生菌屎肠球菌(EF)进行治疗。对内窥镜活检组织进行RNA提取,并对NLRP3、胱天蛋白酶-1(casp-1)、IL-1β和IL-18进行逆转录定量PCR。进行免疫组织化学以研究组织中的蛋白质表达。CE样本中casp-1和NLRP3的基因表达低于对照。用EF进行体外处理可降低对照样本中NLRP3的表达。用EF联合饮食干预治疗CE犬对基因表达没有影响。相比之下,CE中IL-1β蛋白表达随饮食治疗而降低(但益生菌治疗无此效果)。本研究结果表明,炎性小体或其成分可能部分参与了CE中所见的炎症过程,但与人类肠道炎症不同。