Adrenomedullin suppresses interleukin-1β-induced tumor necrosis factor- α production in Swiss 3T3 cells

Yoshitaka Isumi, Atsushi Kubo, Takeshi Katafuchi, Kenji Kangawa, Naoto Minamino

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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 languageEnglish (US)
Pages (from-to)110-114
Number of pages5
JournalFEBS Letters
Volume463
Issue number1-2
DOIs
StatePublished - 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

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