| Autor: |
I P Horan, Helen Parfrey, Stuart N. Farrow, A J Langton, Edwin R. Chilvers, D W Riches |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
Thorax. 65:A16-A17 |
| ISSN: |
0040-6376 |
| DOI: |
10.1136/thx.2010.150912.30 |
| Popis: |
Introduction TNFα is a pleiotropic cytokine that can exert opposing biological actions, either pro-inflammatory or pro-apoptotic, through interaction with its cognate receptor TNF-R1. How this balance is regulated remains to be elucidated. One possible regulator is the novel TNF-R1 interacting protein TRUSS (TNF-R1 ubiquitous signalling and scaffold protein). Ectopic expression of TRUSS activates the transcription factors NF-κB and AP-1. Aims To determine the physiological role of TRUSS in TNFα-TNF-R1 signal transduction. Methods Human epithelial (A549) cells were transfected with human TRUSS siRNA and responses to TNFα stimulation were assessed by RT-PCR, ELISA, immunoblotting and confocal microscopy. Results TRUSS knockdown impaired secretion of the inflammatory chemokines IL-6 and IL-8 following prolonged TNFα stimulation. The maximal reduction of IL-8 mRNA and protein occurred after 12 h of TNFα incubation in the TRUSS deficient cells (p Conclusions Our data suggest TRUSS is integral to TNFα-TNF-R1 mediated NF-κB activation. We propose that TRUSS functions as a scaffold protein involved in the proteasomal processing of p105 into the p50 subunit. Inhibition of this process impairs the nuclear translocation of NF-κB and the consequent p65/p50 regulated gene transcription. Hence, TRUSS may be a novel target for modulating the inflammatory functions of TNFα-TNF-R1 signalling. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
