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Gation. P2Y1 Receptor Source Colonoscopy was performed working with a flexible digital ureteroscope around the day 7 of DSS remedy. For a full description, see SI Components and Techniques. BM Chimeric Mice. Mice receiving BM transfer had been irradiated (900 radiation absorbed dose) quickly prior to transplantation. BM was harvested from femurs and tibias of 4-wk-old SAMP or AKR mice. To get a full description, see SI Materials and Approaches. Myeloperoxidase Assay Activity. Colon samples have been assayed for myeloperoxidase (MPO) activity as previously described (31, 32). For any full description, see SI Components and Strategies. Salmonella Infection Assays. Salmonella infection assays have been performed as previously described (9). For a complete description, see SI Materials and Strategies. Salmonella Infection in Vivo. SAMP and AKR manage mice (four wk) had been infected with Salmonella for two d. To get a complete description, see SI Components and Procedures. Statistical Analysis. Analyses of continuous data had been carried out working with parametric Student t tests, one-way or two-way ANOVAs, or linear regression (when acceptable), or their nonparametric alternatives. For a complete description, see SI Components and Approaches. ACKNOWLEDGMENTS. We thank Prof. Maria Grazia Cifone (University of L’Aquila) for scientific help; Dr. Marcello Chieppa for assistance with bone marrow chimeric mice; Dr. Amitabh Chak for assist together with the mouse colonoscopy; and Li-Guo Jia, Mitchell Guanzon, Dennis Gruszka, Sarah Kossak, Lindsey Kaydo, and Homer Craig for their technical assistance. This perform was supported by National Institutes of Wellness Grants DK091222 (to F.C.), DK055812 (to F.C.), DK042191 (to F.C. and T.T.P.), and DK082437 (to C.M.), also because the Howard Hughes Medical Institute “Med into Grad” Initiative.1. Gutierrez O, et al. (2002) Induction of Nod2 in myelomonocytic and intestinal epithelial cells by way of nuclear factor-kappa B activation. J Biol Chem 277(44):417011705. two. Girardin SE, et al. (2003) Nod2 is usually a common sensor of peptidoglycan via muramyl dipeptide (MDP) detection. J Biol Chem 278(11):8869872. three. Inohara N, et al. (2003) Host recognition of bacterial muramyl dipeptide mediated by means of NOD2. Implications for Crohn’s illness. J Biol Chem 278(8):5509512. four. Inohara N, Nu z G (2003) NODs: Intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol 3(5):37182. five. Kim JY, Omori E, Matsumoto K, N��ez G, Ninomiya-Tsuji J (2008) TAK1 can be a central mediator of NOD2 signaling in epidermal cells. J Biol Chem 283(1):13744. 6. Park JH, et al. (2007) RICK/RIP2 mediates innate immune responses induced by way of Nod1 and Nod2 but not TLRs. J Immunol 178(four):2380386. 7. Wagner CS, Cresswell P (2012) TLR and nucleotide-binding oligomerization domain-like receptor signals differentially regulate exogenous antigen presentation. J Immunol 188(2): 68693. eight. Cooney R, et al. (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16(1):907. 9. Homer CR, Richmond AL, Rebert NA, Achkar JP, McDonald C (2010) ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn’s illness pathogenesis. Gastroenterology 139(five):1630641. ten. Hampe J, et al. (2001) Association in Akt Purity & Documentation between insertion mutation in NOD2 gene and Crohn’s disease in German and British populations. Lancet 357(9272):1925928. 11. Hugot JP, et al. (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s illness. Nature 411(6837):59903. 12. Ogu.

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