| Summary: | Background: Caveolin-1 (Cav-1), the major component of caveolae, is a multifunctional scaffolding protein that serves as a platform for the cell’s signal-transduction and plays a role in inflammation. However, its role in inflammatory bowel disease (IBD), a chronic inflammatory condition in the gastrointestinal tract, is not clear. A recent study shows that Cav-1 mediates angiogenesis in dextran sodium sulphate (DSS)-induced colitis. These results contradict our data, in which Cav-1 levels decreased significantly in 2,4,6-trinitrobenzene sulphonic acid (TNBS)–induced colitis.
Methods: To test whether Cav-1 is involved in IBD pathogenesis, various models representing different dominant Th subtype responses and mimicking the immune pathologic mechanisms of different clinical IBD setting were employed: acute colitis was induced by intra-rectal administration of a single dose of TNBS in BALB/c and C57BL/6J mice, or by drinking 3% DSS water for 6 days in C57BL/6J mice. Chronic colitis was induced by administration of TNBS once a week for 7 weeks in BALB/c mice. To assess the effects of complete loss of Cav-1, Cav-1 knock-out (Cav-1-/-) and control wild-type C57BL/6J mice received a single TNBS administration. To further test the possible role of Cav-1, one of two peptides (that either mimicked (Caveolin scaffolding domain; CSD) or antagonized (Caveolin-1 binding domain; CBD1) Cav-1)) was administered intraperitoneally to mice receiving TNBS. Body weight and clinical scores were monitored. Colon Cav-1 and pro-inflammatory cytokine levels were quantified by ELISA. Inflammation was evaluated through histological analysis.
Results: Cav-1 levels in mouse colon tissue were significantly decreased in TNBS-induced colitis mice when compared to normal mice and also inversely correlated with colon inflammation and cytokine levels. Furthermore, a loss of Cav-1 (Cav-1-/-) showed increased clinical and inflammatory scores and increased body weight loss. Mice receiving peptides to alter Cav-1 levels, showed surprising effects. The mimicking peptide (CSD) showed decreased Cav-1 levels, while the antagonizing peptide (CBD1) showed increased Cav-l levels. These changes in levels were associated with clinical and inflammatory scores and body weight loss that supported the TNBS-induced data. DSS-induced colitis mice showed increased disease activity index, however no significant difference in Cav-1 levels was found between colitis and normal mice.
Conclusions: Cav-1 plays an important role in the protection of TNBS-induced colitis, but not in DSS-induced colitis, an entirely different result from a previous report, suggesting that enhancement of Cav-1 expression and functions may be beneficial to IBD treatment in some specific clinical settings. Further studies are warranted.
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