ERK is an anti-inflammatory signal that suppresses expression of NF-κB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells

Yong Sun Maeng, Jeong Ki Min, Jeong Hun Kim, Akiko Yamagishi, Naoki Mochizuki, Ja Young Kwon, Yong Won Park, Young Myeong Kim, Young Guen Kwon

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Unveiling of endothelial nuclear factor-κB (NF-κB) activation is pivotal for understanding the inflammatory reaction and the pathogenesis of inflammatory vascular diseases. We here report the novel function of extracellular signal-related kinase (ERK) in controlling endothelial NF-κB activation and inflammatory responses. In human endothelial cells, vascular endothelial growth factor (VEGF) induced NF-κB-dependent transcription of cell adhesion molecules (CAMs) and monocyte adhesion. These effects were prominently enhanced by either pretreatment with the MEK inhibitors, PD98059 and U0126 or overexpression of a dominant negative form of MEK, but blocked by a wild type ERK. Consistently, inhibition of ERK significantly increased IκB kinase (IKK) activity, IκBα phosphorylation, and nuclear translocation of NF-κB induced by VEGF, whereas overexpression of ERK resulted in the loss of these responses to VEGF. Using two PKC inhibitors has demonstrated that VEGF concomitantly stimulates IKK and its negative regulatory signal ERK through PKC that lies downstream of KDR/Flk-1. Strikingly, elevation of ERK in endothelial cells markedly inhibited CAM expression and NF-κB activation as well as monocyte adhesion induced by IL-1β and TNF-α. The data collectively suggest that ERK serves as an anti-inflammatory signal that suppresses expression of NF-κB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells. Measuring the existence of ERK activity in vascular endothelial cells may be useful for predicting the feasibility and potency of inflammatory reactions in the vasculature.

Original languageEnglish
Pages (from-to)994-1005
Number of pages12
JournalCellular Signalling
Volume18
Issue number7
DOIs
Publication statusPublished - 2006 Jul 1

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Anti-Inflammatory Agents
Phosphotransferases
Endothelial Cells
Genes
Vascular Endothelial Growth Factor A
Mitogen-Activated Protein Kinase Kinases
Cell Adhesion Molecules
Monocytes
Interleukin-1
Vascular Diseases
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Maeng, Yong Sun ; Min, Jeong Ki ; Kim, Jeong Hun ; Yamagishi, Akiko ; Mochizuki, Naoki ; Kwon, Ja Young ; Park, Yong Won ; Kim, Young Myeong ; Kwon, Young Guen. / ERK is an anti-inflammatory signal that suppresses expression of NF-κB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells. In: Cellular Signalling. 2006 ; Vol. 18, No. 7. pp. 994-1005.
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ERK is an anti-inflammatory signal that suppresses expression of NF-κB-dependent inflammatory genes by inhibiting IKK activity in endothelial cells. / Maeng, Yong Sun; Min, Jeong Ki; Kim, Jeong Hun; Yamagishi, Akiko; Mochizuki, Naoki; Kwon, Ja Young; Park, Yong Won; Kim, Young Myeong; Kwon, Young Guen.

In: Cellular Signalling, Vol. 18, No. 7, 01.07.2006, p. 994-1005.

Research output: Contribution to journalArticle

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AU - Mochizuki, Naoki

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