Regulation of prostaglandin synthesis and cell adhesion by a tryptophan catabolizing enzyme.
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AbstractBACKGROUND: 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.
CitationBMC Biochem. 2001 May 17; 2:5
- Modulation of cellular tryptophan metabolism in human fibroblasts by transforming growth factor-beta: selective inhibition of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase gene expression.
- Authors: Yuan W, Collado-Hidalgo A, Yufit T, Taylor M, Varga J
- Issue date: 1998 Oct
- Immune cell proliferation is suppressed by the interferon-gamma-induced indoleamine 2,3-dioxygenase expression of fibroblasts populated in collagen gel (FPCG).
- Authors: Sarkhosh K, Tredget EE, Karami A, Uludag H, Iwashina T, Kilani RT, Ghahary A
- Issue date: 2003 Sep 1
- Temperature-sensitive polymer-conjugated IFN-gamma induces the expression of IDO mRNA and activity by fibroblasts populated in collagen gel (FPCG).
- Authors: Sarkhosh K, Tredget EE, Uludag H, Kilani RT, Karami A, Li Y, Iwashina T, Ghahary A
- Issue date: 2004 Oct
- Inhibition of indoleamine 2,3-dioxygenase augments trinitrobenzene sulfonic acid colitis in mice.
- Authors: Gurtner GJ, Newberry RD, Schloemann SR, McDonald KG, Stenson WF
- Issue date: 2003 Dec
- The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-gamma in vivo.
- Authors: Burke F, Knowles RG, East N, Balkwill FR
- Issue date: 1995 Jan 3