Induction of pulmonary indoleamine 2,3-dioxygenase by interferon.

Abstract

Pulmonary indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase(decyclizing)] has been found to be induced (30-to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [Yoshida, R. & Hayaishi, 0. (1978) Proc NatL AcadS Sci USA 75,[3998][3999][4000] [4084][4085][4086].In the present study, an in vitro system with mouse lung slices was developed in which bacterial endotoxin (5 ,ug/ml) produced an induction (approximately 10-fold) ofindoleamine 2,3-dioxygenase. The endotoxin was substituted by interferon from mouse L cells or mouse brain. The pulmonary enzyme activity increased almost linearly for 48 hr after addition of mouse interferon (104 units/ ml) to lung slices. Interferon from mouse L cells or mouse brain produced a 10-to 15-fold increase in the enzyme activity, whereas that from human leukocytes was all but ineffective. The effect also was observed using highly purified L-cell interferon, prepared by poly(U) affinity column chromatography. When interferon was treated either by heat, a'.chymotrypsin, or anti-interferon serum, such increase in the enzyme activity was diminished essentially to the same extent as seen in the antiviral activity. The increase in the enzyme activity was blocked when actinomycin D or cycloheximide was added to the slices before interferon treatment. These results suggest that the enzyme induction was produced by interferon and not by possible contaminants in the interferon preparations.Indoleamine 2,3-dioxygenase [indoleamine:oxygen 2,3-oxidoreductase (decyclizing)] (IDOase) is a hemoprotein (1) that catalyzes the incorporation of the superoxide anion as well as molecular oxygen (2, 3) into the pyrrole moiety of various indoleamine derivatives (4, 5). The pulmonary IDOase is dramatically induced (30-to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [lipopolysaccharide (LPS)] (6) or during virus infection (7). To determine the precise mechanisms of IDOase induction, we developed an in vitro system with lung slices from mice and examined the effects of various substances, including the superoxide anion, indoleamines, and interferons, on the enzyme activity. We report herein that the IDOase activity was increased approximately 10-to 15-fold within 48 hr after the addition ofmouse interferon (104 units/ml) to mouse lung slices. A species-specificity ofinterferons and the effects of inhibitors of protein synthesis are presented also.MATERILS AND METHODS Chemicals. L-[ring-2-'4C]Tryptophan (36 Ci/mol; 1 Ci = 3.7 x 1010 becquerels) was purchased from Commisariat a l'Energie Atomique, France, and was purified by column chromatography with Dowex 50W-X2 (H+ form) (0.5 x 1.0 cm), as described (8). LPS from Escherichia coli 055:B5, prepared by the Westphal method, was from Difco. LPS (2.5-500 .g/ml) was suspended in a nonpyrogenic, isotonic NaCl solution and was stored at 40C in a screw-capped vial. An aliquot (0.1 ml) of the suspension was added to Eagle's minimum essential mediu...

Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase

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IFN-α Directly Promotes Programmed Cell Death-1 Transcription and Limits the Duration of T Cell-Mediated Immunity

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1-Methyl-Tryptophan Can Interfere with TLR Signaling in Dendritic Cells Independently of IDO Activity

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