Effects of vitamin A on proliferation of human distal airway epithelial cells in culture.
Using a serum-free culture method, we investigated the effects of vitamin A on the proliferation of human distal airway epithelial cells. Outgrowth of epithelial cells from lung tissue explants was enhanced by treatment with all-trans retinol at concentrations of 10(-8) to 10(-7) M. The colony-forming activity of cells harvested from the primary culture and replated onto Swiss 3T3 fibroblastic feeders was, in contrast, significantly reduced by 10(-7) M to 10(-5) M retinol. When the primary cells were harvested and subcultured on Primaria plates, population expansion was also inhibited by retinol at 10(-10) to 10(-6) M. We further investigated the cells to determine whether there was any difference in sensitivity to the growth-inhibitory effects of vitamin A between cells from the primary culture incubated with and without retinol. The population increase in cells harvested from the primary culture was inhibited equally in retinol-treated and non-treated cells by subsequent treatment with retinol or retinoic acid, this inhibition being dose-dependent. DNA synthetic activity was also inhibited. Interestingly, both the growth rate and the colony-forming efficiency on feeders were greater in the subculture of cells from the retinol-treated primary culture than in those non-treated. When the cells in the secondary subculture were treated with retinoic acid and replated again, they showed a greater population increase rate than those non-treated. Our results showed that human distal airway epithelial cells isolated from lung tissue were sensitive to the growth-inhibitory effect of vitamin A, but the proliferative potential in some fraction of the epithelial cell population was possibly enhanced by vitamin A treatment.
Shibagaki
T
T
Department of Pathology, University of Tsukuba, Ibaraki, Japan.
Kitamura
H
H
Inayama
Y
Y
Ogata
T
T
Kanisawa
M
M
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003469:Culture; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology*
D014801:Vitamin A; D014212:Tretinoin