Abstract
We demonstrated that adrenomedullin (AM) inhibited interleukin-1β- induced tumor necrosis factor-α (TNF-α) secretion and gene transcription in Swiss 3T3 fibroblasts maximally to 23% and 18% of control, while the other peptides elevating intracellular cAMP levels elicited much weaker effects. AM rapidly reduced the gene transcript level of TNF-α, inducing a maximal effect within 1 h. The inhibitory effect of AM was restored with an AM receptor antagonist as well as a cAMP-dependent protein kinase inhibitor. These findings indicate that AM is a potent and quick suppressor of TNF-α production in Swiss 3T3 cells acting through the cAMP protein kinase A pathway. As TNF-α is a major inflammatory cytokine and stimulates AM production in fibroblasts, AM is deduced to be an autocrine or paracrine factor suppressing inflammation through the inhibition of TNF-α production.
Original language | English (US) |
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Pages (from-to) | 110-114 |
Number of pages | 5 |
Journal | FEBS Letters |
Volume | 463 |
Issue number | 1-2 |
DOIs | |
State | Published - Dec 10 1999 |
Keywords
- Adrenomedullin
- Fibroblast
- Interleukin-1β
- Tumor necrosis factor-α
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology