Up-Regulation of Gamma Interferon Receptor Expression Due toChlamydia-Toll-Like Receptor Interaction Does Not Enhance Signal Transducer and Activator of Transcription 1 Signaling
| Autor: | Kari Ann Shirey, Joo-Yong Jung, Joseph M. Carlin |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Immunology
Lymphocyte Antigen 96 Biology Microbiology Interferon-gamma Transactivation Interferon medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Interferon gamma Chlamydia Phosphorylation Receptor Receptors Interferon Host Response and Inflammation Toll-like receptor HEK 293 cells NF-kappa B Molecular biology Coculture Techniques Toll-Like Receptor 2 Up-Regulation Toll-Like Receptor 4 TLR2 STAT1 Transcription Factor Infectious Diseases Parasitology Signal transduction HeLa Cells Signal Transduction medicine.drug |
| Zdroj: | Infection and Immunity. 74:6877-6884 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00505-06 |
| Popis: | Gamma interferon (IFN-γ)-induced indoleamine dioxygenase (IDO), which inhibits chlamydial replication by reducing the availability of tryptophan, is up-regulated by interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α). The mechanisms by which this occurs include an increase in the synthesis of interferon regulatory factor-1 as well as a nuclear factor-κB (NF-κB)-dependent increase in the expression of IFN-γ receptors (IFN-γR). AlthoughChlamydiais susceptible to IDO, it up-regulates IFN-γR expression to a greater degree than either IL-1β or TNF-α, perhaps through interaction with Toll-like receptors (TLR). The purpose of this study was to determine the mechanism by whichChlamydia psittaciup-regulates IFN-γR expression and evaluate this effect on IDO induction. Infection of HEK 293 cells withC. psittaciincreased IFN-γR expression only in cells expressing either TLR2 or TLR4 and the adaptor protein MD-2. In addition, up-regulation of IFN-γR expression inChlamydia-infected HeLa cells could be blocked either by neutralizing TLRs with anti-TLR2 and/or anti-TLR4 or by inhibiting NF-κB transactivation with a proteasome inhibitor. Although the newly expressed IFN-γR inChlamydia-infected cells were capable of binding IFN-γ, they did not enhance IFN-γ-induced IDO activity in a manner similar to those observed for IL-1β and TNF-α. Instead, IDO activation inChlamydia-infected cells was no different than that induced in uninfected cells, despite the increase in IFN-γR expression. Furthermore, the amount of IFN-γ-induced signal transducer and activator of transcription 1 (STAT-1) activation in infected cells paralleled that observed in uninfected cells, suggesting that STAT-1 activation by these newly expressed receptors was impaired. |
| Databáze: | OpenAIRE |
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