Celery & Green Peppers Flavonoid Reduce Brain Inflammati

1 post / 0 new
Celery & Green Peppers Flavonoid Reduce Brain Inflammati

Jang S, Kelley KW, Johnson RW. Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci U S A. 2008 May 19.
PMID: 18490655



Published online on May 19, 2008
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0802865105

Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1
Saebyeol Jang*,, Keith W. Kelley*,,,, and Rodney W. Johnson*,,,¶
*Division of Nutritional Sciences, Integrative Immunology and Behavior Program, Department of Animal Sciences, and Department of Pathology, University of Illinois at Urbana–Champaign, 1207 West Gregory Drive, Urbana, IL 61801
Communicated by David H. Baker, University of Illinois at Urbana–Champaign, Urbana, IL, March 25, 2008 (received for review January 31, 2008)

Luteolin, a flavonoid found in high concentrations in celery and green pepper, has been shown to reduce production of proinflammatory mediators in LPS-stimulated macrophages, fibroblasts, and intestinal epithelial cells. Because excessive production of proinflammatory cytokines by activated brain microglia can cause behavioral pathology and neurodegeneration, we sought to determine whether luteolin also regulates microglial cell production of a prototypic inflammatory cytokine, IL-6. Pretreatment of primary murine microlgia and BV-2 microglial cells with luteolin inhibited LPS-stimulated IL-6 production at both the mRNA and protein levels. To determine how luteolin inhibited IL-6 production in microglia, EMSAs were performed to establish the effects of luteolin on LPS-induced binding of transcription factors to the NF-B and activator protein-1 (AP-1) sites on the IL-6 promoter. Whereas luteolin had no effect on the LPS-induced increase in NF-B DNA binding activity, it markedly reduced AP-1 transcription factor binding activity. Consistent with this finding, luteolin did not inhibit LPS-induced degradation of IB- but inhibited JNK phosphorylation. To determine whether luteolin might have similar effects in vivo, mice were provided drinking water supplemented with luteolin for 21 days and then they were injected i.p. with LPS. Luteolin consumption reduced LPS-induced IL-6 in plasma 4 h after injection. Furthermore, luteolin decreased the induction of IL-6 mRNA by LPS in hippocampus but not in the cortex or cerebellum. Taken together, these data suggest luteolin inhibits LPS-induced IL-6 production in the brain by inhibiting the JNK signaling pathway and activation of AP-1 in microglia. Thus, luteolin may be useful for mitigating neuroinflammation.

cytokines | flavonoids | MAPK | brain | neuroinflammation

Author contributions: S.J., K.W.K., and R.W.J. designed research; S.J. performed research; S.J. analyzed data; and S.J. and R.W.J. wrote the paper.
The authors declare no conflict of interest.
¶To whom correspondence should be addressed. E-mail:

© 2008 by The National Academy of Sciences of the USA

Copyright © 2008 by the National Academy of Sciences