| Autor: |
J J, Lorenz, P J, Furdon, J D, Taylor, M W, Verghese, G, Chandra, T A, Kost, S A, Haneline, L A, Roner, J G, Gray |
| Rok vydání: |
1995 |
| Předmět: |
|
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950). 155(2) |
| ISSN: |
0022-1767 |
| Popis: |
IL-1 beta is a cytokine generally considered to be a major component involved in the pathogenesis of rheumatoid arthritis and other inflammatory diseases. Of the agents found in high concentrations in inflamed rheumatoid arthritis joints, TNF-alpha is among the most strongly implicated as an in vivo inducer of IL-1 beta. Here we report that in human PBMC and in a stable transfectant of the promonocytic cell line, THP-1, TNF-alpha indeed appears to be an inducer of IL-1 beta production, but only in the presence of dibutyryl cAMP or agents such as the PG that elevate intracellular cAMP levels. This TNF-alpha/cAMP pathway regulates IL-1 beta production at the level of transcription and requires a cAMP response element located between -2762 and -2755 bp in the upstream regulatory sequence of IL-1 beta. Because PG, which are known to elevate cAMP levels in vivo, and TNF-alpha are both found in significant quantities in the synovial fluid of rheumatoid arthritis joints, the observed synergistic up-regulation in IL-1 beta synthesis by TNF-alpha/cAMP (PG) may provide valuable insight into the potential pathways involved in the continuous production of IL-1 beta in the chronically inflamed joint. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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