Premium
Anti‐inflammatory Actions and Mechanisms of γ‐Tocotrienol in Lipopolysaccharide‐stimulated Macrophages
Author(s) -
Wang Yun,
Jiang Qing
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.904.2
Subject(s) - lipopolysaccharide , p38 mitogen activated protein kinases , chemistry , nitric oxide , cytokine , mapk/erk pathway , nitric oxide synthase , signal transduction , cyclooxygenase , prostaglandin e2 , phosphorylation , inflammation , microbiology and biotechnology , pharmacology , macrophage , biochemistry , biology , immunology , enzyme , endocrinology , in vitro , organic chemistry
We have shown that gamma‐tocopherol (γ‐T), the major form of vitamin E in US diet, possesses anti‐inflammatory activity by inhibition of cyclooxygenase‐2 (COX‐2) catalyzed prostaglandin E 2 (PGE 2 ) synthesis in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophages. Here in the same cellular system we investigated potential anti‐inflammatory activity of gamma‐tocotrienol (γ‐TE), another vitamin E form with unsaturated hydrophobic side chain. γ‐TE at as low as 5 µM inhibited LPS‐activated PGE 2 and dose‐dependently reduced nitrite accumulation, but had no effect on cell viability or LPS‐induced expression of COX‐2 or inducible nitric oxide synthase. γTE inhibited LPS‐stimulated interleukin‐6 (IL‐6), an pro‐inflammatory cytokine, in a dose‐dependent manner, but had no effect on interlukine 10, an anti‐inflammatory cytokine. Mechanistic studies indicated that in this cellular system, COX‐2 expression is regulated by p38 MAPK signaling pathway, while IL‐6 is regulated by NFkB. Consistently, γTE treatment did not show any effect on phosphorylation of p38, but rather resulted in an inhibition of phosphorylation of IkBa, a key event during NFkB activation. Studies are undertaken to further understand the molecular target/mechanism and anti‐inflammatory actions of γTE. (Supported by R01AT001821, P01AT002620 and P50AT000477) Grant Funding Source By R01AT001821, P01AT002620 and P50AT000477