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Adrenomedullin signals through NF‐κB in epithelial cells
Author(s) -
Pleguezuelos Olga,
Hagi-Pavli Eleni,
Crowther George,
Kapas Supriya
Publication year - 2004
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/j.febslet.2004.10.019
Subject(s) - adrenomedullin , nf κb , western blot , microbiology and biotechnology , p50 , transcription factor , nfkb1 , chemistry , biology , signal transduction , peptide , biochemistry , gene
Adrenomedullin is a peptide found in a variety of cells and tissues and involved in a multitude of biological processes. Recently, adrenomedullin has been identified as a host defense peptide and as such it plays a role in the inflammatory response. The transcription factor NF‐κB is a major regulator of genes involved in the inflammatory response and the aim of this study was to determine whether NF‐κB played a role in the inflammatory process triggered by adrenomedullin. Skin epithelial cells (HaCaTs) were used as our model in vitro. Western blot analysis from adrenomedullin‐stimulated HaCaT cells revealed a rapid degradation of NF‐κB inhibitor α and β followed by the translocation of free NF‐κB to the nucleus, where it was detected by Texas Red immunostaining after incubation with adrenomedullin for 15 min. Electromobility shift assay showed that NF‐κB present in the nucleus was active, since it bound to a probe containing an NF‐κB binding site. Supershift assays indicated that p50 and p65, members of the NF‐κB family, were both part of the NF‐κB dimmers involved in adrenomedullin cell signaling. HaCaTs secreted interleukin‐6 in response to AM, which was significantly attenuated by the NF‐κB inhibitor SN‐50. Taken together, the data lend support for an immunoregulatory role for AM.