Global Suppression of IL-6-induced Acute Phase Response Gene Expression after Chronic in Vivo Treatment with the Peroxisome Proliferator-activated Receptor-α Activator Fenofibrate

Abstract

The peroxisome proliferator-activated receptor ␣ (PPAR␣), which is highly expressed in liver, plays key roles in lipid metabolism and inflammation. Interleukin-6 (IL-6) is the principal inducer of acute phase response (APR) gene expression. In the present study, we demonstrate that chronic treatment with the PPAR␣ agonist fenofibrate fully prevents the IL-6-induced APR gene expression in wild-type but not in PPAR␣-

Statins and nitric oxide reduce C-reactive protein production while inflammatory conditions persist

“…We have not yet measured such complexes in SNP-treated cells. STAT3 was also shown to mediate the inhibitory effect of fenofibrates on CRP expression (Gervois et al, 2004). However, we found that neither the STAT3-site nor the B-site was involved in mediating the NO effects.…”

Fenofibrate and PBA prevent fatty acid-induced loss of adiponectin receptor and pAMPK in human hepatoma cells and in hepatitis C virus-induced steatosis

“…Interestingly, fenofi brate reversed HCV-mediated impairment of AMPK and AdipoR2 expression in Huh.8 cells but did not affect TG levels. Fenofi brate reduced the palmitateinduced activation of C/EBP ␤ and pJNK while increasing PPAR ␣ protein expression and this supports the role of fenofi brate in reducing ER stress and activation of infl ammatory genes found in earlier studies ( 33,(65)(66)(67). While chronic high-fat feeding in mice has been shown to both decrease ( 49 ) and increase ( 68 ) …”

Vesicular Stomatitis Virus Expressing Tumor Suppressor p53 Is a Highly Attenuated, Potent Oncolytic Agent

“…IL-6 can act as a proinflammatory cytokine that signals through the IL-6r␣-gp130 receptor complex and activates JAKs, which in turn activate a number of STAT molecules (23). IL-6 is also the primary mediator of the acute-phase fever response and could be a component of inflammatory responses seen with increased doses of rVSV (19). IP-10 (CXCL10) levels were also reduced in the sera of VSV-M(mut)-mp53-treated mice.…”