Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages.
10.4196/kjpp.2016.20.4.415
- Author:
Young An BAE
1
;
Hyae Gyeong CHEON
Author Information
1. Department of Microbiology, Gachon University School of Medicine, Incheon 21936, Korea.
- Publication Type:Original Article
- Keywords:
Activating transcription factor-3;
Berberine;
Inflammation;
Lipopolysaccharide;
Macrophage
- MeSH:
Activating Transcription Factor 3*;
AMP-Activated Protein Kinases;
Animals;
Berberine*;
Cytokines;
Endotoxemia;
Hand;
Inflammation;
Interleukin-6;
Lung;
Macrophages*;
Mice;
Phosphorylation;
Plasma;
RNA, Messenger;
Spleen
- From:The Korean Journal of Physiology and Pharmacology
2016;20(4):415-424
- CountryRepublic of Korea
- Language:English
-
Abstract:
Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction.
