Rat alveolar type II cells inhibit lung fibroblast proliferation in vitro

Fibroblasts stimulate alveolar type II epithelial cell differentiation and proliferation in vitro and during lung development. However, little is know n about the effects of adult type II cells on fibroblasts. We investigated the effect of adult rat type II cells on proliferation of adult human lung fibroblasts. Fibro blasts were suspended within rat tail collagen which was gelled on a floating polycarbonate filter, and type II cells were cultured on Matrigel. In this coculture system, alveolar type II cells inhibited fi broblast proliferation and indomethacin blocked the inhibitory effect on fi broblast growth. Prostaglandin (PG) E-2, the major PG secreted by type II c ells, inhibited fibroblast proliferation and was increased during the perio d of inhibition of fibroblast proliferation. Incubation with arachidonate s howed that most of the PGE(2) in the coculture system was produced by the f ibroblasts. In addition, we found that rat type II cells also inhibited rat fibroblasts and that inhibition of fibroblast growth by type II cells coul d be stimulated by keratinocyte growth factor. We conclude that in this coc ulture system, type II cells inhibit fibroblast proliferation by secreting a factor(s) that stimulates PGE(2) production by fibroblasts, and that PGE( 2) directly inhibits fibroblast proliferation.