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

FEBS Letters

Minamino, Naoto¹  Kubo, Atsushi¹  Kangawa, Kenji¹  Katafuchi, Takeshi¹  Isumi, Yoshitaka¹ 

[1] National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan

关键词: Adrenomedullin;    Tumor necrosis factor-α;    Interleukin-1β;    Fibroblast;    AM;    adrenomedullin;    TNF;    tumor necrosis factor;    IL;    interleukin;    LPS;    lipopolysaccharide;    PKA;    cAMP-dependent protein kinase;    EC;    endothelial cell;    VSMC;    vascular smooth muscle cell;    CGRP;    calcitonin gene-related peptide;   

DOI  :  10.1016/S0014-5793(99)01615-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown