Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling |
| |
Authors: | Kavita Bisht Barbara Wegiel Jens Tampe Oliver Neubauer Karl-Heinz Wagner Leo E Otterbein Andrew C Bulmer |
| |
Institution: | 1. Heart Foundation Research Center, Griffith Health Institute, Griffith University, Gold Coast, Australia;2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA;3. Griffith Enterprise, Griffith University, Nathan, Australia;4. Emerging Field Oxidative Stress and DNA Stability and Research Platform Active Aging, Department of Nutritional Science, University of Vienna, Vienna, Austria |
| |
Abstract: | Macrophages play a crucial role in the maintenance and resolution of inflammation and express a number of pro- and anti-inflammatory molecules in response to stressors. Among them, the complement receptor 5a (C5aR) plays an integral role in the development of inflammatory disorders. Biliverdin and bilirubin, products of heme catabolism, exert anti-inflammatory effects and inhibit complement activation. Here, we define the effects of biliverdin on C5aR expression in macrophages and the roles of Akt and mammalian target of rapamycin (mTOR) in these responses. Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Biliverdin also reduced LPS-dependent expression of the pro-inflammatory cytokines TNF-α and IL-6. Collectively, these data indicate that biliverdin regulates LPS-mediated expression of C5aR via the mTOR pathway, revealing an additional mechanism underlying biliverdin’s anti-inflammatory effects. |
| |
Keywords: | ANOVA analysis of variance BCA bicinchoninic acid FACS fluorescence-activated cell sorting GAPDH glyceraldehyde 3-phosphate dehydrogenase HPRT hypoxanthine-guanine phosphoribosyltransferase M-CSF macrophage-colony stimulating factor NF-κB nuclear factor kappa B qRT-PCR quantitative real time polymerase chain reaction |
本文献已被 ScienceDirect 等数据库收录! |
|