Proliferation of rat and human lung fibroblasts following exposure to prostaglandin E2

Numerous investigators have reported that exogenous prostaglandin E2 (PGE2) can inhibit human lung fibroblast proliferation in vitro. Yet various lines of evidence derived from clinical and experimental studies suggest that PGE2 may not be of major importance in inhibiting fibroblast proliferation in vivo. We examined the effects of exogenously-supplied PGE2 on the in vitro proliferation of HFL-1 human lung fibroblasts and rat lung fibroblasts derived from Fischer 344 rats using a multisample assay system that provided a detailed kinetic picture of PGE2 effects on fibroblast proliferation. Exogenously supplied PGE2 (5-5000 ng/ml) had no effect on the proliferation of actively cycling or initially quiescent subconfluent populations of rat lung fibroblasts. In contrast, initially quiescent subconfluent or confluent cultures of HFL-1 cells that were treated with 50-5000 ng/ml PGE2 exhibited a dose-dependent, transitory inhibition of division when stimulated to return to a state of active proliferation. Once division resumed, the cells divided at the rate of the PGE2-free control condition, even in the continued presence of the prostaglandin. This initial postinhibitory resumption of division was not attributable to the emergence of a PGE2-resistant subpopulation. Thus, although exogenously supplied PGE2 indeed inhibits proliferation of human pulmonary fibroblasts in vitro, the duration of the inhibition appears to be much shorter than previously suspected.