N. MDP (by means of NOD2) activation is known to be protective within this acute colitis model (19). DSS-treated SAMP and AKR manage mice were administered MDP (100 g or PBS, i.p.) for three consecutive days (days 0, 1, and 2 of colitis induction) to assess the protective effects of MDP within this model of colitis. As shown in Fig. 1A, AKR control mice administered MDP lost substantially significantly less body weight than AKR mice receiving PBS. In contrast, SAMP mice treated with MDP exhibited comparable body fat loss to SAMP mice treated with PBS. Physique weight correlated with myeloperoxidase activity evaluated in colons of treated mice (Fig. 1B), and with all the histological assessment of colitis (Fig. 1C). Colonoscopy revealed that, in AKR mice, a lot more serious inflammation was linked with PBS therapy, demonstrated by increased inflammatory cellular infiltrates within the lamina propria, whereas MDP-treated mice showed only mild inflammation with slight vascular changes and granularity. In SAMP mice, extreme inflammation, such as marked wall thickening, irregular vascular patterns, fibrin, granularity, and bleeding, was observed in mice treated with both PBS and MDP (Fig. 1D). Representative histological sections are shown in Fig. 1E. These information suggest that the previously reported in vivo protective effects of MDP against DSS-induced murine colitis are also observed in AKR control mice, but not in SAMP mice, suggestingFig. 1. MDP administration in vivo reduces DSS colitis in AKR mice, but not in SAMP mice. SAMP and AKR mice had been treated with three DSS in their drinking water for 7 d (n = eight?1 per group). At the early phase of colitis induction (days 0, 1, 2), mice have been administered either MDP (100 g, i.p.) or PBS everyday. (A) Modifications in body weight in SAMP and AKR mice administered MDP or PBS (two-way ANOVA repeated measures, MDP protective effect for AKR was significant at P = 0.023, but not for SAMP, P = 0.1256355-53-9 Chemscene 125).674799-96-3 Purity (B) Myeloperoxidase (MPO) activity calculated from the colons of treated mice (Kruskal?Wallis, P 0.01, Dunn’s). (C) Colonic total inflammatory scores, as determined by the sum of chronic inflammation, active inflammation, percentage reepithelialization, and percentage of ulceration (one-way ANOVA, P 0.001; pairwise Bonferroni). (D) High-resolution endoscopic images of the proximal colon right after 7 d of DSS treatment show extreme inflammation in both groups of SAMP mice (PBS and MDP) and mild inflammation (which includes slight vascular modifications and mild granularity) in AKR manage mice treated with MDP compared with PBS.PMID:24914310 (E) Representative histopathological sections show active, severe ulcers, adjacent regenerative crypts, active cryptitis, and increased inflammatory cells in the lamina propria of SAMP mice treated with PBS and MDP. Sections from AKR mice treated with MDP show regenerative colonic mucosa with focal mild, active cryptitis, and much more minimal improved inflammatory cells compared with PBS-treated AKR mice. (Scale bars, 100 m.) Data are represented as mean ?SEM. The single asterisk (*), double asterisk (**), and triple asterisk (***) denote important variations at P 0.05, P 0.01, and P 0.001, respectively. Benefits are representative of 3 independent experiments.17000 | pnas.org/cgi/doi/10.1073/pnas.Corridoni et al.that SAMP mice have an abnormal innate immune response to MDP administration.Defective Function of NOD2 Signaling in SAMP Mice Is Derived from Hematopoietic Sources. Simply because NOD2 is an intracellular PRRexpressed in a restricted quantity o.
