title: Expression of interferon regulatory factors and indoleamine 2,3-dioxygenase in Chlamydia trachomatis-infected synovial fibroblasts.
abstract: Synovial fibroblasts probably represent host cells for Chlamydia trachomatis during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-beta (IFN-beta) in response to chlamydial infection. IFN-beta expression can be activated by interferon regulatory factor-1 (IRF-1) and interferon-stimulated gene factor 3gamma (ISGF3gamma). In this study, we demonstrate that infection of synovial fibroblasts with C. trachomatis serotype D induced the expression of IRF-1 mRNA as shown by reverse transcription-PCR. Tumor necrosis factor-alpha (TNF-alpha) stimulation enhanced IRF-1 mRNA levels in infected cells and was required to detect IRF-1 protein by immunoblotting. The level of constitutively expressed IRF-2 was not significantly affected after infection. C. trachomatis was found to cause an up-regulation of ISGF3gamma protein in synovial cells. Induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellular infection by chlamydiae. It has been described that IRF-1 can induce IDO gene expression. Infection of synovial fibroblasts alone in the absence of exogenous cytokine induced the expression of IDO mRNA which was enhanced by TNF-alpha treatment. The stimulation of IRF-1, ISGF3gamma, and IDO expression was most effective when viable chlamydiae were used as inoculum. Neutralization of IFN-beta in the culture medium of infected cells diminished but did not abrogate expression of IRF-1, ISGF3gamma, and IDO. The increased production of IRF-1 and ISGF3gamma in C. trachomatis-infected synovial fibroblasts may contribute to induction of IFN-beta and IDO.
authors.affiliation: Institute of Medical Microbiology, Friedrich Schiller University of Jena, Germany. Roedel@bach.med.uni-jena.de
authors.forename: J
authors.initials: J
authors.lastname: Rödel
authors.forename: A
authors.initials: A
authors.lastname: Groh
authors.forename: M
authors.initials: M
authors.lastname: Hartmann
authors.forename: K H
authors.initials: KH
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Lehmann
authors.forename: W
authors.initials: W
authors.lastname: Lungershausen
authors.forename: E
authors.initials: E
authors.lastname: Straube
mesh_terms: D000906:Antibodies / Q000276:immunology; D001426:Bacterial Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D002692:Chlamydia trachomatis / Q000187:drug effects / Q000254:growth & development*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D015151:Immunoblotting; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050856:Interferon Regulatory Factor-1; D016899:Interferon-beta / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis; D010750:Phosphoproteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology*; D014364:Tryptophan / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000906:Antibodies; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D014364:Tryptophan; D014366:Tryptophan Oxygenase