Induction of tryptophan 2, 3-dioxygenase expression in human monocytic leukemia/lymphoma cell lines THP-1 and U937. (December 2019)

• Record Type: Journal Article
• Authors: Hoffmann, Delia; Pilotte, Luc; Stroobant, Vincent; Van den Eynde, Benoit J
• Is Part Of: International journal of tryptophan research. Volume 12(2019)
• Publication Date: 2019-12
• Subjects: Tryptophan 2, 3-dioxygenase -- PMA -- PKC -- monocyte -- IFN-gamma -- LPS; Biochemistry -- Periodicals; Tryptophan -- Periodicals; Tryptophan; Biochemical Phenomena; Biochemistry; Tryptophan; Electronic journals; Periodicals; Periodicals; 572.65
• DOI: 10.1177/1178646919891736
• Languages: English
• ISSNs: 1178-6469

Abstract

Tumor-associated macrophages are immune cells with diverse functions in tumor development. Among other functions, they downregulate immune-mediated tumor rejection by depriving lymphocytes of nutrients. The essential amino acid tryptophan is metabolized by the enzymes indoleamine 2, 3-dioxygenase 1 and tryptophan 2, 3-dioxygenase (TDO). Indoleamine 2, 3-dioxygenase 1 is expressed in a large number of human tumors, and inhibitors are in development to improve immunotherapy. Tryptophan 2, 3-dioxygenase was also found in human tumors and preclinical working models confirmed its immunosuppressive power. We explored a potential expression of TDO by macrophages. This enzyme could be induced in two human cell lines, THP-1 and U937, by incubation with phorbol myristate acetate, lipopolysaccharide, and interferon gamma. Phorbol-myristate-acetate-mediated induction was inhibited by rottlerin, a protein kinase C inhibitor. In contrast to these monocytic cell lines, other cell lines or fresh human monocytes isolated from peripheral blood mononuclear cells and differentiated into proinflammatory or anti-inflammatory macrophages could not be induced to express TDO. Our results suggest that TDO might play an immunosuppressive role in human monocytic leukemias but not in untransformed macrophages.