2d). Thus, although the macroscopic inflammation of colonic tissue was similar in both DSS-treated wild-type and Bcl-3−/− mice, the clinical indices of the DSS-induced colitis, in particular weight loss, were reduced significantly Selleck NU7441 in Bcl-3−/− mice. To investigate further the differences in DSS-induced colitis between wild-type and Bcl-3−/− mice, we performed a histological examination of distal colon tissue sections from untreated and DSS-treated wild-type and Bcl-3−/− mice (Fig. 3a). No differences were observed between untreated wild-type and untreated Bcl-3−/− distal colonic tissue samples by H&E staining. Both wild-type

and Bcl-3−/− mice displayed normal epithelial architecture with intact goblet cells and BAY 57-1293 manufacturer crypts with no discernible

inflammatory influx. DSS treatment of wild-type mice induced a dramatic alteration in the colonic mucosal tissue with extensive oedema, large cellular infiltrates and a severe loss of tissue organization with destruction of crypts and loss of goblet cells. Although histological analysis revealed similar levels of oedema and cellular infiltrates in Bcl-3−/− mice, there was significantly less destruction of the tissue architecture following DSS treatment (Fig. 3a). Quantitative histopathological analysis of the distal colon tissue from DSS-treated Bcl-3−/− mice revealed significantly reduced epithelium damage and loss of tissue architecture compared to wild-type mice (Fig. 3b). However, there were no significant differences in the extent of inflammation (Fig. 3c) and the degree of cellular Low-density-lipoprotein receptor kinase infiltration and oedema (Fig. 3d) between DSS-treated wild-type and Bcl-3−/− mice. This histological analysis

provides insight into the reduced weight loss and overall clinical disease score observed in DSS-treated Bcl-3−/− mice relative to wild-type mice, which would appear to result from an intact or regenerated epithelium rather than reduced leucocyte infiltration. Although histological analysis showed similar levels of oedema and leucocyte infiltration in DSS-treated wild-type and Bcl-3−/− mice, it is possible that the inflammation may be qualitatively different between these groups. In order to characterize the inflammation associated with DSS-induced colitis in Bcl-3−/− mice, we next measured inflammatory gene expression in distal colon tissue from untreated and DSS-treated wild-type and Bcl-3−/− mice using qRT–PCR. Surprisingly, although Bcl-3 has been described previously as a negative regulator of Toll-like receptor-induced proinflammatory gene expression, we found no significant difference in the expression of TNF-α, IL-6, CXCL1 and IL-1β between DSS-treated wild-type and Bcl-3−/− mice (Fig. 4a). Recent studies have identified a protective role for the cytokines IL-17A and IL-22 [22-24] in DSS colitis by inducing anti-bacterial peptide expression and epithelial cell regeneration in the colon.