ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor δ (PPARδ) stimulation

Chang Hoon Woo, Michael P. Massett, Tetsuro Shishido, Seigo Itoh, Bo Ding, Carolyn McClain, Wenyi Che, Sreesatya Raju Vulapalli, Chen Yan, Jun Ichi Abe

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69 Scopus citations

Abstract

Peroxisome proliferator-activated receptors (PPAR) decrease the production of cytokine and inducible nitric-oxide synthase (iNOS) expression, which are associated with aging-related inflammation and insulin resistance. Recently, the involvement of the induction of heme oxygenase-1 (HO-1) in regulating inflammation has been suggested, but the exact mechanisms for reducing inflammation by HO-1 remains unclear. We found that overexpression of HO-1 and [Ru(CO)3Cl2]2, a carbon monoxide (CO)-releasing compound, increased not only ERK5 kinase activity, but also its transcriptional activity measured by luciferase assay with the transfection of the Gal4-ERK5 reporter gene. This transcriptional activity is required for coactivation of PPARδ by ERK5 in C2C12 cells. [Ru(CO)3Cl2] 2 activated PPARδ transcriptional activity via the MEK5/ERK5 signaling pathway. The inhibition of NF-κB activity by ERK5 activation was reversed by a dominant negative form of PPARδ suggesting that ERK5/PPARδ activation is required for the anti-inflammatory effects of CO and HO-1. Based on these data, we propose a new mechanism by which CO and HO-1 mediate anti-inflammatory effects via activating ERK5/PPARδ, and ERK5 mediates CO and HO-1-induced PPARδ activation via its interaction with PPARδ.

Original languageEnglish
Pages (from-to)32164-32174
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number43
DOIs
StatePublished - Oct 27 2006

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    Woo, C. H., Massett, M. P., Shishido, T., Itoh, S., Ding, B., McClain, C., Che, W., Vulapalli, S. R., Yan, C., & Abe, J. I. (2006). ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor δ (PPARδ) stimulation. Journal of Biological Chemistry, 281(43), 32164-32174. https://doi.org/10.1074/jbc.M602369200