Caveolin‐1 regulation of experimental colitis

Inflammatory bowel disease and experimental models of colitis display microvascular dysfunction which contributes to colon tissue pathology. Recent studies demonstrate that caveolin‐1 may be important in regulating microvascular function and inflammatory responses. However, the pathological role of caveolin‐1 in experimental colitis is unknown. Here we subjected wild‐type and caveolin‐1−/− (Cav‐1−/−) mice to the 3 % Dextran Sulfate Sodium (DSS) model of experimental colitis. Analysis of weight change, stool consistency, occult blood, and evidence of gross bleeding showed a significant decrease in disease activity index (DAI) in Cav‐1−/− mice compared to wild‐type control mice. Moreover, examination of tissue histopathology showed significant protection in Cav‐1−/− colons. In wild type colons, complete crypt dropout and transmural inflammation was observed with primarily lymphoplasmacytic infiltrate along with scattered neutrophils and the degree of inflammation ranging from severe to mild depending on disease severity. In contrast, DSS mediated histopathology was significantly diminished in Cav‐1−/− colons. DSS induced colitis was also evaluated in wild type mice treated with an AP‐Cav‐AB peptide (3 mg/kg) corresponding to the caveolin‐1 scaffolding domain. Interestingly, the AP‐Cav‐AB peptide significantly attenuated DSS DAI and histopathology scores compared to control peptide treated mice. These data identify a novel pathway whereby caveolin‐1 plays an important regulatory role during the development of experimental colitis.