title: Tumor necrosis factor-alpha and lipopolysaccharide enhance interferon-induced antichlamydial indoleamine dioxygenase activity independently.
abstract: In macrophages, interleukin-1 (IL-1) and lipopolysaccharide (LPS) enhance the antichlamydial effect of interferon-gamma (IFN-gamma) by increasing indoleamine 2,3-dioxygenase (IDO) activity in a dose-dependent manner. Our objectives were to characterize the antichlamydial effect of tumor necrosis factor-alpha (TNF-alpha) on IFN-induced IDO activity and to establish the relationship between LPS and TNF-alpha in IDO potentiation. TNF-alpha inhibited chlamydial growth in a dose-dependent manner only in IFN-treated macrophages. Furthermore, excess tryptophan reversed the effect of combined cytokine treatment, indicating that IDO alone was responsible for chlamydial inhibition. The promonocyte THP-1 cell line, previously used to model the effect of IL-1 on IDO mRNA expression, was treated with IFN-gamma and increasing concentrations of LPS or TNF-alpha. IDO mRNA was quantified by RT-PCR, and IDO activity was measured by HPLC at 24 and 48 h after treatment, respectively. Both LPS and TNF-alpha enhanced IDO activity and IDO mRNA expression, with maximal IDO induction at 100 ng/ml LPS or 5 ng/ml TNF-alpha. Anti-TNF-alpha failed to neutralize the effects of LPS treatment, and insufficient TNF-alpha or IL-1 was produced by LPS-treated THP-1 cells to account for the enhancing effect of LPS, indicating that the effect of LPS on IDO was independent of TNF-alpha and IL-1.
authors.affiliation: Department of Microbiology, Miami University, Oxford, OH 45056, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Currier
authors.forename: M H
authors.initials: MH
authors.lastname: Ziegler
authors.forename: M M
authors.initials: MM
authors.lastname: Riley
authors.forename: T A
authors.initials: TA
authors.lastname: Babcock
authors.forename: V P
authors.initials: VP
authors.lastname: Telbis
authors.forename: J M
authors.initials: JM
authors.lastname: Carlin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002691:Chlamydophila psittaci / Q000201:enzymology* / Q000254:growth & development* / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D004790:Enzyme Induction / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000900:Anti-Bacterial Agents; D006131:Growth Inhibitors; D007106:Immune Sera; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase