Mesothelial cell modulation of pleural repair: thrombin stimulated mesothelial cells release prostaglandin E2.
Repair of an injured pleura without fibrosis not only requires a re-establishment of the normal pleural mesothelial monolayer but also a downregulation of the inflammatory response, including inhibition of fibroblast proliferation and collagen synthesis. However, the role of the mesothelial cell in regulating these processes in the pleural space remains undefined. We therefore hypothesized that mesothelial cells, stimulated by thrombin, release prostaglandin E2 PGE2, which is capable of inhibiting fibroblast proliferation. In vitro rat visceral mesothelial cells were exposed to thrombin and PGE2 levels in the supernatant were measured using a competitive radioimmunoassay. Our results demonstrated that mesothelial cells produce PGE2 in a dose- and time-dependent manner. In addition, both anti-thrombin 3 and indomethacin completely blocked the PGE2 released. Finally, conditioned media from thrombin-stimulated mesothelial cells inhibited fibroblast [3H]thymidine incorporation. These results demonstrate that the mesothelial cell is capable of contributing to the repair process of pleural injury by the release of a local factor such as PGE2.
Department of Medicine, Veterans Administration Medical Center, Indianapolis, Indiana.
J W
JW
Hott
S W
SW
Godbey
V B
VB
Antony
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D007700:Kinetics; D010995:Pleural Diseases / Q000473:pathology / Q000503:physiopathology*; D010998:Pleurisy / Q000517:prevention & control; D051381:Rats; D013917:Thrombin / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D003094:Collagen; D013917:Thrombin; D015232:Dinoprostone