Abstract:
:Persistent tumour necrosis factor alpha (TNF-alpha) exposure uncouples proximal T-cell receptor (TCR)-signalling events. Here, we demonstrate that chronic TNF-alpha exposure also attenuates signalling distal to the TCR, by specifically inhibiting Ca2+ influx evoked by thapsigargin in CD4+ T-cells. Mitogen-induced Ca2+ responses were impaired in a dose dependent manner, and TCR-induced Ca2+ responses were also significantly reduced. The impairment of Ca2+ influx strongly correlated with poor function as proliferative responses to both mitogen and anti-CD3/CD28 stimulation were suppressed. Our findings show that persistent TNF-alpha exposure of T-cells specifically inhibits store operated Ca2+ influx. This may affect gene activation and contribute to the poor T-cell function in chronic inflammatory disease.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Church LD,Goodall JE,Rider DA,Bacon PA,Young SPdoi
10.1016/j.febslet.2005.01.051keywords:
subject
Has Abstractpub_date
2005-02-28 00:00:00pages
1539-44issue
6eissn
0014-5793issn
1873-3468pii
S0014-5793(05)00152-3journal_volume
579pub_type
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