1-ALPHA,25-DIHYDROXYVITAMIN-D-3 RAPIDLY INHIBITS FIBROBLAST-INDUCED COLLAGEN GEL CONTRACTION

1 alpha a,25-Dihydroxyvitamin D-3 (1,25-D-3) inhibits the proliferatio n of fibroblasts in vitro in monolayer culture, We investigated the ef fect of 1,25-D-3 on normal murine and human fibroblasts cultured in co llagen type I gels, which more closely resembles the in vivo situation in the dermis, In this culture system 1,25-D-3 had no effect on fibro blast proliferation; however, the fibroblast-induced collagen gel cont raction was inhibited in a time- and concentration-dependent manner in the nanomolar concentration range. 25-Hydroxyvitamin D-3 and 24,25-di hydroxyvitamin D-3 were inactive, 1,25-D-3 had no effect in fibroblast s lacking a functional vitamin D receptor, Pretreatment of fibroblasts in monolayer culture for 5 min was sufficient to trigger the inhibiti on of collagen gel contraction, Nifedipine increased collagen gel cont raction and counteracted the effect of 1,25-D-3. The inhibition of col lagen gel contraction by 1,25-D-3 is supposed to be mediated by the vi tamin D receptor because a functional vitamin D receptor is required, and vitamin D metabolites with low affinity to the vitamin D receptor were inactive, Brief pretreatment of fibroblasts was sufficient to tri gger the inhibitory effect of 1,25-D-3, suggesting a nongenomic effect . A genomic mode of action could not be ruled out, however, because th e inhibition was first measured after 24 h. The antagonism of the calc ium channel antagonist nifedipine probably represents the sum of two o pposite effects rather than supporting evidence for a nongenomic mode of action of 1,25-D-3. In conclusion, 1,25-D-3 has a specific and rapi dly triggered inhibitory effect on fibroblast-induced collagen gel con traction.