Journal article
INTERFERON-γ UP-REGULATES TOLL-LIKE RECEPTOR 4 AND COOPERATES WITH LIPOPOLYSACCHARIDE TO PRODUCE MACROPHAGE-DERIVED CHEMOKINE AND INTERFERON-γ INDUCIBLE PROTEIN-10 IN HUMAN BLADDER CANCER CELL LINE RT4
The Journal of urology, Vol.174(3), pp.1119-1123
2005
DOI: 10.1097/01.ju.0000168619.25341.96
PMID: 16094077
Abstract
Previously we have reported that RT4, a well differentiated human bladder cancer line, increases the expression of macrophage derived chemokine (MDC) and interferon (IFN)-γ-inducible protein-10 (IP-10) in response to IFN-γ and tumor necrosis factor (TNF)-α. In this study we examined the signal mechanisms for inducting these 2 chemokines in RT4 cells by lipopolysaccharide (LPS), IFN-γ and TNF-α.
MDC and IP-10 expression was evaluated by sandwich enzyme-linked immunosorbent assay. Signal molecule activation was examined by Western blotting and electrophoretic mobility shift assay. The expression of toll-like receptor (TLR)-4 was analyzed by reverse transcriptase-polymerase chain reaction and flow cytometry.
LPS did not induce RT4 cells to produce IP-10 and MDC. However, LPS plus IFN-γ synergized the productions of the 2 chemokines. IFN-γ up-regulated the expression of TLR-4, which is an LPS binding receptor. Although LPS and IFN-γ alone marginally activated nuclear factor (NF)-κB but not AP-1, LPS plus IFN-γ augmented NF-κB and AP-1. Specific inhibition of NF-κB and AP-1 pathways decreased the production of MDC and IP-10. Extracellular regulated kinase (ERK)1/2, an upstream signal of AP-1, was also responsive to LPS and/or IFN-γ. TNF-α also activated NF-κB, AP-1 and ERK1/2. However, TNF-α plus IFN- γ was associated with the activation of NF-κB but not of AP-1/ERK1/2 for the induction of MDC and IP-10.
IFN-γ enhances LPS for the induction of MDC and IP-10 through up-regulation of TLR-4, and the signal pathways of NF-κB and AP-1/ERK1/2. This mechanism may help us understand inflammatory responses of the bladder to localized bacterial infection.
Details
- Title: Subtitle
- INTERFERON-γ UP-REGULATES TOLL-LIKE RECEPTOR 4 AND COOPERATES WITH LIPOPOLYSACCHARIDE TO PRODUCE MACROPHAGE-DERIVED CHEMOKINE AND INTERFERON-γ INDUCIBLE PROTEIN-10 IN HUMAN BLADDER CANCER CELL LINE RT4
- Creators
- HIROSHI Yamada - University of IowaMICHAEL A. OdonnellTETSURO Matsumoto - University of IowaY.I. Luo - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of urology, Vol.174(3), pp.1119-1123
- Publisher
- Elsevier Inc
- DOI
- 10.1097/01.ju.0000168619.25341.96
- PMID
- 16094077
- ISSN
- 0022-5347
- eISSN
- 1527-3792
- Language
- English
- Date published
- 2005
- Academic Unit
- Urology
- Record Identifier
- 9984319991402771
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