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Fish Oil Modulates Macrophage P44/P42 Mitogen‐Activated Protein Kinase Activity Induced By Lipopolysaccharide
Author(s) -
Lo ChongJeh,
Chiu Ken C.,
Fu Minjuan,
Chu Audrey,
Helton Scott
Publication year - 2000
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607100024003159
Subject(s) - mapk/erk pathway , lipopolysaccharide , protein kinase a , kinase , electrophoretic mobility shift assay , tumor necrosis factor alpha , proinflammatory cytokine , microbiology and biotechnology , biology , chemistry , biochemistry , transcription factor , inflammation , endocrinology , immunology , gene
Background: Mitogen‐activated protein kinase (MAPK) cascades represent a major signal system to transduce extracellular signals into cellular responses. Overactivity of MAPK has been implicated in the development of many diseases, including cancer and sepsis. This study investigated the hypothesis that fish oil altered the membrane phospholipid composition and modulated MAPK activity. Methods: RAW 264.7 cells, a mouse macrophage (M(ϕ) cell line, were grown in eicosapentaenoic acid (EPA)‐rich media (114 μmol/L) for 48 hours. Mϕ were washed and exposed to Escherichia coli lipopolysaccharide (LPS; 1 μg/mL) for 10 minutes. Both total and activated (phosphorylated) portions of MAPK (P44 and P42) were determined by Western blot assays. AP‐1 transcription factor activity was determined by electrophoretic mobility gel shift assays (EMSA). Mϕ tumor necrosis factor (TNF) mRNA expression was measured by Northern blot assays. Results: LPS stimulation induced RAW cell phosphorylation of P44/P42. In contrast, RAW cells grown in EPA‐rich media had less P44/P42 activation in the presence of LPS. Total P44/P42 were not affected by EPA or LPS. Similarly, EPA also inhibited AP‐1 activity. Inhibition of P44/P42 activity with PD98059 reduced both AP‐1 activity and TNF mRNA expression of LPS‐stimulated Mϕ. Conclu sions: Our data suggest that fish oil regulates macrophage proinflammatory gene activation, at least in part, by modulating the MAPK activity. (Journal of Parenteral and Enteral Nutrition 24:159–163, 2000)