Apocynin inhibits Toll-like receptor-4-mediated activation of NF-κB by suppressing the Akt and mTOR pathways

Microbial product lipopolysaccharide has been shown to be involved in the pathogenesis of inflammatory skin diseases. Apocynin has demonstrated to have an anti-inflammatory effect. However, the effect of apocynin on the Toll-like receptor-4-dependent activation of Akt, mammalian target of rapamycin (mTOR), and nuclear factor (NF)-kappa B pathway, which is involved in productions of inflammatory mediators in keratinocytes, has not been studied. Using human keratinocytes, we investigated the effect of apocynin on the inflammatory mediator production in relation to the Toll-like receptor-4-mediated-Akt/mTOR and NF-kappa B pathways, which regulates the transcription genes involved in immune and inflammatory responses. Apocynin, Akt inhibitor SH-5, Bay 11-7085 and N-acetylcysteine each attenuated the lipopolysaccharide-induced production of cytokines, PGE(2), and chemokines, changes in the levels of Toll-like receptor-4, p-Akt, mTOR, and NF-kappa B, and production of reactive oxygen species in keratinocytes. The results show that apocynin appears to attenuate the lipopolysaccharide-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor-4-mediated activation of the Akt, mTOR, and NF-kappa B pathways. The effect of apocynin appears to be attributed to its inhibitory effect on the production of reactive oxygen species. Apocynin appears to attenuate the microbial product-mediated inflammatory skin diseases.