MESOTHELIAL CELL MODULATION OF PLEURAL REPAIR - THROMBIN-STIMULATED MESOTHELIAL CELLS RELEASE PROSTAGLANDIN E(2)

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).