Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Autor(en)
Kavita Bisht, Barbara Wegiel, Jens Tampe, Oliver Neubauer, Karl-Heinz Wagner, Leo E Otterbein, Andrew C Bulmer
Abstrakt

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.

Organisation(en)
Department für Ernährungswissenschaften
Externe Organisation(en)
Harvard University, Griffith University
Journal
Biochemical and Biophysical Research Communications
Band
449
Seiten
94-99
Anzahl der Seiten
6
ISSN
0006-291X
DOI
https://doi.org/10.1016/j.bbrc.2014.04.150
Publikationsdatum
06-2014
Peer-reviewed
Ja
ÖFOS 2012
303009 Ernährungswissenschaften
Schlagwörter
ASJC Scopus Sachgebiete
Molecular Biology, Biophysics, Biochemistry, Cell Biology
Link zum Portal
https://ucrisportal.univie.ac.at/de/publications/biliverdin-modulates-the-expression-of-c5ar-in-response-to-endotoxin-in-part-via-mtor-signaling(da9b0298-1511-4b57-9a80-47cb6ceea519).html