Skip to main content
eScholarship
Open Access Publications from the University of California

UC San Diego

UC San Diego Previously Published Works bannerUC San Diego

Anti-inflammatory Actions of Acanthoic Acid-Related Diterpenes Involve Activation of the PI3K p110γ/δ Subunits and Inhibition of NF-κB

Abstract

The effect of acanthoic acid analogs on the response to proinflammatory challenge was investigated. Some pimarane diterpenes are known activators of the LXRαβ nuclear receptors, but we show here that they also exert a rapid, potent, and selective activation of the p110γ and p110δ subunits of PI3K. Combination of these effects results in an important attenuation of the global transcriptional response to LPS in macrophages. PI3K/Akt activation leads to inhibition of the LPS-dependent stimulation of IKK/NF-κB and p38 and ERK MAPKs. Macrophages from LXRαβ-deficient mice exhibited an inhibition of these pathways similar to the corresponding wild-type cells. Silencing or inhibition of p110γ/δ suppressed the effect of these diterpenes (DTPs) on IKK/NF-κB and MAPKs signaling. Taken together, these data show a multitarget anti-inflammatory mechanism by these DTPs including a selective activation of PI3K isoenzymes. Diterpenes exert anti-inflammatory effects broadly impacting the NF-κB pathway, and Través etal. now show selective activation of the p110γ/δ PI3K isoforms in macrophages by a class of acanthoic-acid related molecules. © 2014 Elsevier Ltd.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View