Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 89, Issue 1, Pages 105-111Publisher
WILEY
DOI: 10.1189/jlb.0610355
Keywords
inflammation; MAPK; ferulaldehyde
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Funding
- Hungarian Science Research Fund [K-73738, F-67996]
- Innovation Research Team [TAMOP-4.2.2-08/1/2008-0011]
- ETT [281/2009]
- AOKKA [34039-1/2009]
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Macrophages represent the first defense line against bacterial infection and therefore, play a crucial role in early inflammatory response. In this study, we investigated the role of MAPKs and MKP-1 activation in regulation of an early inflammatory response in RAW 264.7 macrophage cells. We induced the inflammatory response by treating the macrophages with LPS and inhibited an early inflammatory response by using ferulaldehyde, a water-soluble end-product of dietary polyphenol degradation that we found previously to exert its beneficial anti-inflammatory effects during the early phase of in vivo inflammation. We found that LPS-induced ROS and nitrogen species formations were reduced by ferulaldehyde in a concentration-dependent manner, and ferulaldehyde protected mitochondria against LPS-induced rapid and massive membrane depolarization. LPS induced early suppression of MKP-1, which was accompanied by activation of JNK, ERK, and p38 MAPK. By reversing LPS-induced early suppression of MKP-1, ferulaldehyde diminished MAPK activation, thereby inhibiting NF-kappa B activation, mitochondrial depolarization, and ROS production. Taken together, our data suggest that ferulaldehyde exerts its early anti-inflammatory effect by preserving the mitochondrial membrane integrity and shifting the expression of MKP-1 forward in time in macrophages. J. Leukoc. Biol. 89: 105-111; 2011.
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