Effects of retinoids on human bronchial epithelial cells: differential regulation of hyaluronate synthesis and keratin protein synthesis.

Respiratory tract epithelia are one type of tissue targeted by vitamin A. In this study the effects of vitamin A and its analogs (retinoids) on human bronchial epithelial (HBE) cells have been investigated in a serum-free hormone-supplemented medium. This serum-free medium, which was developed for the long-term cultivation of protease-dissociated HBE cells, consists of Ham's F12 nutrient medium supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, cholera toxin, and bovine hypothalamus extract. Under these in vitro conditions, retinoids specifically stimulate the synthesis and secretion of hyaluronate (HA) and alter the pattern of synthesis of keratin proteins. In regard to HA, the degree of stimulation ranges from two-fold to ten-fold and is concentration dependent. In regard to keratin proteins, the most prominent effects of retinoids are inhibition of synthesis of the 48 kd and 50 kd keratin proteins (corresponding to cytokeratins 16 and 14, respectively, in the catalog of human cytokeratins; Moll et al., 1982) and stimulation of synthesis of the 40 kd and 52-54 kd proteins. The data indicate that retinoid effects on HA and keratin protein synthesis occur at different levels. The stimulation of HA synthesis occurs immediately after the addition of retinoid and cannot be prevented by pretreatment with actinomycin D, whereas the alterations in the pattern of keratin protein synthesis appear later and are inhibited by treatment with actinomycin D at or before the administration of retinoid. This study demonstrates that HBE cultures maintained in the serum-free condition can serve as an in vitro model to elucidate the mechanisms of retinoid actions.