Novel CATERPILLER gene involved in mucosal inflammation

描述(申请人提供)：卡特彼勒蛋白含有N-末端效应结构域、核苷酸结合域和一系列富含亮氨酸的重复序列。这些蛋白在免疫反应中很重要，疾病与几种蛋白有关，包括MHCT2A、Clas和NOD2/CARD15。NOD2/CARD15的突变只与克罗恩病患者的一部分有关。克罗恩病和溃疡性结肠炎是一种复杂的慢性疾病，称为炎症性肠病(IBD)。目前的学说认为，IBD是由于对肠道地方性微生物群的异常免疫反应所致。我们筛选了几个新的卡特彼勒基因的表达谱，以确定这些基因在IBD小鼠模型中是否受到影响。在SPF条件下饲养的IL10-/-小鼠的结肠和盲肠中，16.1/NOD27表达上调(约100倍)。16.1/NOD27表达上调与横结肠自发分泌IL-12相关。对16.1/NOD27的生化分析表明，它是一种依赖于NF-K B的基因表达的调节因子。这些数据表明16.1/NOD27在活动性结肠炎相关的炎症反应中发挥了作用。

DESCRIPTION (provided by applicant): CATERPILLER proteins contain N-terminal effector domains, a nucleotide binding domain and a series of leucine rich repeats. These proteins are important in immune responses and disease associations have been linked to several, including MHCT2A, ClAS and NOD2/CARD15. Mutations in NOD2/CARD15 are associated exclusively with a subset of Crohn's disease patients. Crohn's disease and ulcerative colitis are complex and chronic disorders that are referred to as inflammatory bowel disease (IBD). Current dogma suggests that IBD results from aberrant immune responses to endemic microflora of the gut. We screened the expression profile of several novel CATERPILLER genes to determine if these genes were influenced in a mouse model for IBD. 16.1/NOD27 was shown to be upregulated ( approximately 100 fold) in the colon and cecum of ILl0-/-mice reared under SPF conditions relative to GF animals. Upregulation of 16.1/NOD27 correlated with spontaneous ex vivo IL-12 secretion of the transverse colon. Biochemical analysis of 16.1/NOD27 has shown it to be a regulator of NF-K B dependent gene expression. These data suggest a role for 16.1/NOD27 in the inflammatory response associated with active colitis.