Paradoxical effects of a synthetic metalloproteinase inhibitor that blocks both p55 and p75 TNF receptor shedding and TNF alpha processing in RA synovial membrane cell cultures.

@article{Williams1996ParadoxicalEO,
  title={Paradoxical effects of a synthetic metalloproteinase inhibitor that blocks both p55 and p75 TNF receptor shedding and TNF alpha processing in RA synovial membrane cell cultures.},
  author={Lynn M. Williams and Deena L Gibbons and Andrew J. H. Gearing and Ravinder N. Maini and Marc Feldmann and Fionula Mary Brennan},
  journal={The Journal of clinical investigation},
  year={1996},
  volume={97 12},
  pages={2833-41}
}
We have previously hypothesized that the pro-inflammatory cytokine TNF alpha has a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It mediates its effects by cross-linking surface p55 TNF receptors (TNF-R), which can be proteolytically cleaved to yield soluble fragments. Upon binding TNF alpha soluble TNF-R (sTNF-R) can inhibit its function. We investigated the enzymatic nature of the proteases involved in TNF-R cleavage, and found that this process is blocked by a synthetic… CONTINUE READING

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