Lycopene suppresses proinflammatory response in lipopolysaccharide-stimulated macrophages by inhibiting ROS-induced trafficking of TLR4 to lipid raft-like domains

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T1 - Lycopene suppresses proinflammatory response in lipopolysaccharide-stimulated macrophages by inhibiting ROS-induced trafficking of TLR4 to lipid raft-like domains

AU - Zou, Jun

AU - Feng, Dan

AU - Ling, Wen-Hua

AU - Duan, Rui-Dong

PY - 2013

Y1 - 2013

N2 - We recently showed that lycopene inhibited lipopolysaccharide (LPS)-induced productions of nitric oxide (NO) and interleukin-6 (IL-6) in murine RAW264.7 macrophages by mechanisms related to inhibition of ERK and nuclear factor-kappa B. Since the assembly of Toll-like receptor 4 (TLR4) in lipid rafts is a key element in LPS induced signaling, we investigated whether this process would be influenced by lycopene. We found that pretreatment of RAW264.7 cells with lycopene inhibited LPS-induced recruitment of TLR4 into fractions - enriched with lipid raft marker. By the methods of immunoprecipitation and immunoblotting, we also found that lycopene inhibited the subsequent formation of the complex of TLR4 with its adaptors including myeloid differentiation primary-response protein 88 and TIR domain-containing adaptor-inducing IFN-beta. We also found that the lycopene induced inhibition was associated with reduced formation of reactive oxygen species (ROS), which was an upstream mechanism for the effects of lycopene, because treating the cells with the antioxidant N-acetyl-L-cysteine and NADPH oxidase inhibitor diphenyleneiodonium chloride significantly inhibited LPS-induced recruitment of TLR4 into lipid raft-like domains as well as the production of proinflammatory molecule NO and IL-6. Thus, our findings suggest that lycopene may prevent LPS-induced TLR4 assembly into lipid rafts through reducing intracellular ROS level. (C) 2013 Elsevier Inc. All rights reserved.

AB - We recently showed that lycopene inhibited lipopolysaccharide (LPS)-induced productions of nitric oxide (NO) and interleukin-6 (IL-6) in murine RAW264.7 macrophages by mechanisms related to inhibition of ERK and nuclear factor-kappa B. Since the assembly of Toll-like receptor 4 (TLR4) in lipid rafts is a key element in LPS induced signaling, we investigated whether this process would be influenced by lycopene. We found that pretreatment of RAW264.7 cells with lycopene inhibited LPS-induced recruitment of TLR4 into fractions - enriched with lipid raft marker. By the methods of immunoprecipitation and immunoblotting, we also found that lycopene inhibited the subsequent formation of the complex of TLR4 with its adaptors including myeloid differentiation primary-response protein 88 and TIR domain-containing adaptor-inducing IFN-beta. We also found that the lycopene induced inhibition was associated with reduced formation of reactive oxygen species (ROS), which was an upstream mechanism for the effects of lycopene, because treating the cells with the antioxidant N-acetyl-L-cysteine and NADPH oxidase inhibitor diphenyleneiodonium chloride significantly inhibited LPS-induced recruitment of TLR4 into lipid raft-like domains as well as the production of proinflammatory molecule NO and IL-6. Thus, our findings suggest that lycopene may prevent LPS-induced TLR4 assembly into lipid rafts through reducing intracellular ROS level. (C) 2013 Elsevier Inc. All rights reserved.

KW - Lycopene

KW - TLR4

KW - ROS

KW - LPS

KW - RAW264.7 cells

U2 - 10.1016/j.jnutbio.2012.08.011

DO - 10.1016/j.jnutbio.2012.08.011

M3 - Article

VL - 24

SP - 1117

EP - 1122

JO - Nutrition Reports International

T2 - Nutrition Reports International

JF - Nutrition Reports International

SN - 1873-4847

IS - 6

ER -