Flavone apigenin has an anti-inflammatory effect. We assessed whether apigenin may reduce the inflammatory mediator production, which is regulated by the Toll-like receptor-4-dependent activation of the Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK in HEK001 keratinocytes and primary keratinocytes. Apigenin, the Akt inhibitor, Bay 11-7085, and N-acetylcysteine inhibited the lipopolysaccharide-stimulated production of cytokines IL-1β and IL-6 and chemokines CCL17 and CCL27; the expression of cyclooxygenase-2; the increase in the levels of Toll-like receptor-4, phosphorylated Akt, and mTOR; the activation of NF-κB; the activation of the JNK and p38-MAPK; and the production of reactive oxygen/nitrogen species in keratinocytes. Inhibitors of the c-JNK (SP600125) and p38-MAPK (SB203580) reduced lipopolysaccharide-induced production of inflammatory mediators and activation of the JNK and p38-MAPK in keratinocytes. These results show that apigenin may inhibit the lipopolysaccharide-caused inflammatory mediator production in keratinocytes by reducing the Toll-like receptor-4-dependent activation of Akt, mTOR, and NF-κB pathways, and activation of JNK and p38-MAPK. The suppressive effect of apigenin may be achieved by the inhibition of reactive oxygen/nitrogen species production. Additionally, apigenin appears to reduce the Akt, mTOR, and NF-κB pathway- and the JNK and p38-MAPK-mediated inflammatory skin diseases.
Keywords: Akt, mTOR, and NF-κB pathways; Apocynin; Inflammatory mediator production; JNK and p38-MAPK; Keratinocytes; Lipopolysaccharide; Toll-like receptor-4.