Recombinant adeno-associated virus carrying thymosin ß4 suppresses experimental colitis in mice.

AIM: To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin ß4 (AAV-Tß4) on murine colitis via intracolonic administration. METHODS: AAV-Tß4 was prepared and intracolonically used to mediate the secretory expression of Tß4 in mouse colons. Dextran sulfate sodium (DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tß4 on colitis. The activities of myeloperoxidase (MPO) and superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis and proliferation were detected by TUNEL assay and immunochemistry, respectively. RESULTS: Recombinant AAVs efficiently delivered LacZ and Tß4 into the colonic tissues of the mice, and AAV-Tß4 led to a strong expression of Tß4 in mouse colons. In both the DSS and TNBS colitis models, AAV-Tß4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tß4 significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tß4 also modulated colonic TNF-α, IL-1ß and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice. CONCLUSION: Tß4 exerts a protective effect on murine colitis, indicating that AAV-Tß4 could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases.