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Disruption of lipid rafts impairs the production of nitric oxide in lipopolysaccharide-stimulated murine RAW264.7 macrophages

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Upon stimulation with lipopolysaccharide, murine RAW264.7 macrophages generated a high amount of nitric oxide. Pretreatment of macrophages with methyl-β-cyclodextrin, which disrupted the lipid raft microdomains of the plasma membrane, inhibited the generation of nitric oxide by down-regulating the expression of inducible nitric oxide synthase. Methyl-β-cyclodextrin exposure significantly inhibited the degradation of IκB-α, blocked the translocation of p65/RelA into the nuclei and prevented the activation of the NF-κB signaling pathway. The results suggest that the expression of inducible nitric oxide synthase and the consequent production of nitric oxide depend on the integrity of the lipid rafts.


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