Lycopene suppresses LPS-induced NO and IL-6 production by inhibiting the activation of ERK, p38MAPK, and NF-κB in macrophages

Lycopene has antioxidant, anticancer, and anti-inflammatory effects with molecular mechanisms not fully identified. We investigated the effects of lycopene on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. Lycopene inhibited LPS-induced production of nitric oxide (NO) and interleukin-6 (IL-6) with decreased mRNAs of inducible nitric oxide synthase and IL-6 but had no effect on TNF-alpha. Further study showed that lycopene also inhibited LPS-induced I kappa B phosphorylation, I kappa B degradation, and NF-kappa B translocation. Moreover, lycopene blocked the phosphorylation of ERK1/2 and p38 MAP kinase but not c-Jun NH2-terminal kinase. To confirm the causal link between MAP kinase inhibition and its anti-inflammatory effects, we treated the cells with SB 203580 and U0126. These inhibitors significantly inhibited LPS-induced NO and IL-6 formation. Lycopene inhibits the inflammatory response of RAW 264.7 cells to LPS through inhibiting ERK/p38 MAP kinase and the NF-kappa B pathway.