Investigation of the role of hypoxia-inducible factor-1α in myeloid cells in dextran sulfate sodium (DSS)-induced colitis in mice

Abstract

Myeloid-specific Vhlh-deficient mice (Vhlh fl/fl) which hypoxia-inducible factor-1α is constitutively active displayed increased susceptibility to 5% DSS-induced colitis as shown by a greater reduction in body weight, high disease activity index based on rectal bleeding and bloody stool. Although Hif-1α fl/fl mice provided a little protection against the loss of body weight on DSS-induced colitis compared with their wild-type mice, Hif-1α fl/fl mice showed no significant differences in clinical signs of DSS-induced colitis compared with wild-type littermates possibly due to a limited role of hypoxia at onset of colitis. Under conditions of colonic inflammation induced by administration of DSS, recruitment of CD45+ cells and Gr-1+ cells into colon was dramatically increased in Vhlh fl/fl mice. However, there was not significant difference in CD45+ cells and Gr-1+ cells between WT and Hif-1α fl/fl mice. High susceptibility to 5% DSS-induced colitis of Vhlh fl/fl mice may be associated with infiltrates of CD45+ and Gr-1+ inflammatory cell. Our results suggest that deficiency of Vhlh in myeloid cells resulted in deleterious effects on DSS-induced colitis.