Studies of TGF-beta(1-3) in serosal fluid during abdominal surgery and their effect on in vitro human mesothelial cell proliferation.
BACKGROUND
Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation.


METHODS
Total as well as biologically active TGF-beta(1-3) and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-beta(1-3) stimulation was also investigated.


RESULTS
Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation.


CONCLUSIONS
This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.
Falk
Peter
P
Fibrinolysis Laboratory/Tissue Centre, Department of Surgery, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. peter.falk@surgery.gu.se
Bergström
Maria
M
Palmgren
Ingrid
I
Holmdahl
Lena
L
Breimer
Michael E
ME
Ivarsson
Marie-Louise
ML
D000005:Abdomen / Q000601:surgery*; D000368:Aged; D001826:Body Fluids / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000601:surgery; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D004848:Epithelium; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010529:Peritoneal Cavity; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D053781:Transforming Growth Factor beta2 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D053782:Transforming Growth Factor beta3 / Q000097:blood / Q000378:metabolism / Q000494:pharmacology
D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3