Mouse Anti Human Reg3g Hybridoma [DQUD-Sfh4h-5B3]

Supplementary L-tryptophan (L-Trp) limits the decrease of feed intake and growth in Enterotoxigenic Escherichia coli F4 (ETEC) susceptible pigs upon oral challenge with this pathogen. Susceptibility to ETEC is genetically controlled and related to the presence of receptors for the F4 fimbriae (F4R). We aimed to assess if dietary Trp affects genes involved in the intestinal barrier of healthy pigs carrying or not the F4R. Thirty-six littermate weaning pigs were selected to have potentially eighteen ETEC-susceptible and eighteen ETEC-non-susceptible subjects, based on a Mucin 4 gene polymorphism. For 21 days they were fed a diet with 0.17 or 0.22 ileal digestible Trp:Lys ratio. Using the test of ETEC adhesion to the intestinal villi, the pigs were divided into F4R negative (no bacteria adhering, F4R(-)), F4R positive (F4R(+)), and F4R mildly positive (F4R(m+)). A preliminary test (GeneChip (R) Porcine Genome Array) highlighted the differentially expressed genes in the jejunum of 3 F4R- and 3 F4R(+) pigs. The expression of the most interesting genes was assessed on the whole sample. In F4R(+) pigs, Trp reduced the mRNA of four genes involved in the intestinal barrier and/or induced by several bacteria-associated molecular patterns, like lipopolysaccharide (LPS) (REG3G, Regenerating islet-derived 3 gamma; SFTPD, Surfactant pulmonary-associated protein D: CFB, Complement factor 13; LBP, LPS-binding protein) (P< 0.05). In pigs fed the low-Trp diet, REG3G, SFTPD and LPB mRNA increased with F4R presence (P < 0.05). Interleukine-8 tended to be less expressed with the higher Trp level whatever the F4R presence (P=0.09). No DNA from ETEC was detected in the jejunum contents. Trp favorably interacts to reduce the bacterial induction of some genes involved in the intestinal barrier in ETEC susceptible pigs, but the causative mechanism is yet to be established. (C) 2012 Elsevier B.V. All rights reserved.

Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease (IBD) and increases the risk for colorectal cancer. Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice. However, the inflammasome sensor absent in melanoma 2 (AIM2) protects against colorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways. Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined. Here we show that the AIM2 inflammasome has a protective role in the intestine. During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein (IL-22BP) in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides (AMPs) Reg3 beta and Reg3 gamma, which promotes dysbiosis-linked colitis. During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2(-/-) mice promotes excessive IL-22 production and elevated STAT3 activation. Aim2(-/-) mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression. This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2(-/-)mice to colorectal cancer. Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.