Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 10, Pages 7121-7127Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.10.7121
Keywords
-
Categories
Funding
- NHLBI NIH HHS [R01 HL075040-01] Funding Source: Medline
Ask authors/readers for more resources
LPS stimulates monocytes/macrophages through the activation of signaling events that modulate the production of inflammatory cytokines. Apigenin, a flavonoid abundantly found in fruits and vegetables, exhibits anti-proliferative and anti-inflammatory activities through poorly defined mechanisms. In this study, we demonstrate that apigenin inhibits the production of proinflammatory cytokines IL-1 beta, IL-8, and TNF in LPS-stimulated human monocytes and mouse macrophages. The inhibitory effect on proinflammatory cytokine production persists even when apigenin is administered after LPS stimulation. Transient transfection experiments using NF-kappa B reporter constructs indicated that apigenin inhibits the transcriptional activity of NF-kappa B in LPS-stimulated mouse macrophages. The classical proteasome-dependent degradation of the NF-kappa B inhibitor I kappa B alpha was observed in apigenin LPS-stimulated human monocytes. Using EMSA, we found that apigenin does not alter NF-kappa B-DNA binding activity in human monocytes. Instead we show that apigenin, as part of a non-canonical pathway, regulates NF-kappa B activity through hypophosphorylation of Ser536 in the p65 subunit and the inactivation of the IKK complex stimulated by LPS. The decreased phosphorylation on Ser536 observed in LPS-stimulated mouse macrophages treated with apigenin was overcome by the over-expression of IKK beta. In addition, our studies indicate that apigenin inhibits in vivo LPS-induced TNF and the mortality induced by lethal doses of LPS. Collectively, these findings suggest a molecular mechanism by which apigenin suppresses inflammation and modulates the immune response in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available