Regulation of prostaglandin synthesis and cell adhesion by a tryptophan catabolizing enzyme.
BACKGROUND
The tryptophan catabolizing enzyme, indoleamine 2,3, dioxygenase (IDO) is one of two mammalian enzymes, which can catabolize the rarest essential amino acid, tryptophan. IDO is inducible by cytokines such as interferon-gamma and plays a role in inflammation and maternal tolerance of fetal allografts, although its exact mode of action is unclear. Therefore, we investigated the circumstances under which IDO is expressed in vitro together with the effects of overexpression of IDO on the growth and morphology of cells.


RESULTS
Overexpression of IDO in the murine macrophage cell line RAW 264.7 and the murine fibrosarcoma cell line MC57, resulted in the growth of macroscopic cell foci, with altered cell adhesion properties. The expression of IDO was also detected during adhesion of wild type, nontransfected cells in tissue culture to standard cell growth substrates. Inhibition of this expression, likewise resulted in alterations in cell adhesion. Overexpression of IDO or inhibition of endogenous IDO expression was accompanied by changes in metalloproteinase expression and also in the expression and activity of the cyclooxygenase enzymes. In the case of RAW cells, IDO effects on cell growth could be reversed by adding back prostaglandins.


CONCLUSIONS
These results suggest that catabolism of the rarest essential amino acid may regulate processes such as cell adhesion and prostaglandin synthesis.
Marshall
B
B
Program in Molecular Immunology, Institute for Molecular Medicine and Genetics, Medical College of Georgia, CB 2803, 1120 15th Street, Augusta, GA 30912-3175, USA. marshall@immagene.mcg.edu
Keskin
D B
DB
Mellor
A L
AL
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis* / Q000494:pharmacology; D016372:RNA, Antisense / Q000494:pharmacology; D014162:Transfection; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011453:Prostaglandins; D016372:RNA, Antisense; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D008666:Metalloendopeptidases