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Adrenomedullin suppresses interleukin‐1β‐induced tumor necrosis factor‐α production in Swiss 3T3 cells
Author(s) -
Isumi Yoshitaka,
Kubo Atsushi,
Katafuchi Takeshi,
Kangawa Kenji,
Minamino Naoto
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01615-4
Subject(s) - autocrine signalling , adrenomedullin , tumor necrosis factor alpha , cytokine , paracrine signalling , endocrinology , medicine , protein kinase a , inflammation , biology , kinase , receptor , chemistry , microbiology and biotechnology
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.