Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling
| Autor: | Kavita Bisht, Oliver Neubauer, Andrew C. Bulmer, Barbara Wegiel, Karl-Heinz Wagner, Jens Tampe, Leo E. Otterbein |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Lipopolysaccharides
Macrophage GAPDH glyceraldehyde 3-phosphate dehydrogenase Complement receptor 030204 cardiovascular system & hematology Biochemistry Antioxidants chemistry.chemical_compound Mice 0302 clinical medicine FACS fluorescence-activated cell sorting polycyclic compounds ANOVA analysis of variance NF-κB nuclear factor kappa B 0303 health sciences TOR Serine-Threonine Kinases Cell biology mTOR lipids (amino acids peptides and proteins) Signal transduction medicine.symptom Signal Transduction Bilirubin Biophysics Inflammation Biology Article Cell Line 03 medical and health sciences medicine Animals Protein kinase B Receptor Anaphylatoxin C5a Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology Biliverdin qRT-PCR quantitative real time polymerase chain reaction Macrophages Biliverdine NF-κB Cell Biology Macrophage Activation BCA bicinchoninic acid Endotoxins chemistry M-CSF macrophage-colony stimulating factor HPRT hypoxanthine-guanine phosphoribosyltransferase |
| Zdroj: | Biochemical and Biophysical Research Communications |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.04.150 |
| Popis: | Highlights • Biliverdin mitigates LPS-dependent C5aR expression in macrophages in part via mTOR. • Biliverdin promotes phosphorylation of Akt and PS6. • Biliverdin decreases LPS-mediated induction of C5aR-associated cytokines. 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. |
| Databáze: | OpenAIRE |
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