Autocrine stimulation of WI38 cell proliferation in the presence of glucocorticoids. Characteristics of the stimulatory factor(s) involved in this response.
Chronic exposure to hydrocortisone (HC) or dexamethasone (DEX) results in a 20-40% extension in the proliferative lifespan of WI38 cells. Within a single growth cycle, the addition of HC or DEX at seeding results in saturation densities 20-40% higher than in control cultures. We have recently reported that, within a single growth cycle, the proliferative response of WI38 cells to glucocorticoids is mediated by a stimulatory factor(s) present in medium conditioned by cells in the presence of the hormone. We report here that chronic exposure to medium conditioned in the presence of HC for the first 24 h after seeding (24-h HC-conditioned medium (24-h HC-CM)) results in a 25% extension in the proliferative lifespan of these cultures. The generation of the stimulatory factor(s) present in glucocorticoid-conditioned medium is apparently dependent upon undefined cellular alterations which result from the subcultivation-procedure; confluent or low-density quiescent cultures did not generate media stimulatory to cell growth in the presence of glucocorticoids. This response was not trypsin-dependent, since cultures subcultivated in the absence of proteolytic treatment generated media equally stimulatory to cell growth. A further characterization of this glucocorticoid-induced activity revealed the stimulatory factor(s) was of low MW (dialyzable and recoverable in the less than 10,000 MW fraction following ultrafiltration), heat-stable (95 degrees C), and resistant to treatment with trypsin, chymotrypsin, or protease (S. griseus).
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D005347:Fibroblasts / Q000166:cytology*; D006133:Growth Substances / Q000502:physiology*; D006358:Hot Temperature; D006854:Hydrocortisone / Q000494:pharmacology*; D008168:Lung; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000494:pharmacology
D003470:Culture Media; D006133:Growth Substances; D003907:Dexamethasone; D004247:DNA; D010447:Peptide Hydrolases; D006854:Hydrocortisone