Repair of an injured pleura without fibrosis not only requires a re-es
tablishment of the normal pleural mesothelial monolayer but also a dow
nregulation of the inflammatory response, including inhibition of fibr
oblast proliferation and collagen synthesis. However, the role of the
mesothelial cell in regulating these processes in the pleural space re
mains undefined. We therefore hypothesized that mesothelial cells, sti
mulated by thrombin, release prostaglandin E(2) PGE(2), which is capab
le of inhibiting fibroblast proliferation. In vitro rat visceral mesot
helial cells were exposed to thrombin and PGE(2) levels in the superna
tant were measured using a competitive radioimmunoassay. Our results d
emonstrated that mesothelial cells produce PGE(2) in a dose- and time-
dependent manner. In addition, both anti-thrombin 3 and indomethacin c
ompletely blocked the PGE(2) released. Finally, conditioned media from
thrombin-stimulated mesothelial cells inhibited fibroblast [H-3]thymi
dine incorporation. These results demonstrate that the mesothelial cel
l is capable of contributing to the repair process of pleural injury b
y the release of a local factor such as PGE(2).