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

Bisht, Kavita, Wegiel, Barbara, Tampe, Jens, Neubauer, Oliver, Wagner, Karl-Heinz, Otterbein, Leo E., & Bulmer, Andrew C. (2014) Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling. Biochemical and Biophysical Research Communications, 449(1), pp. 94-99.

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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-alpha 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.

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ID Code: 84814
Item Type: Journal Article
Refereed: Yes
Keywords: Inflammation, Macrophage, mTOR
DOI: 10.1016/j.bbrc.2014.04.150
ISSN: 1090-2104
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Cellular Immunology (110704)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > MEDICAL PHYSIOLOGY (111600) > Cell Physiology (111601)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 The Authors
Copyright Statement: This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/)
Deposited On: 23 Jul 2015 22:54
Last Modified: 26 Jul 2015 23:17

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