Inhibition of the Nuclear Factor-κB Signaling Pathway by Leflunomide or Triptolide also Inhibits the Anthralin-Induced Inflammatory Response but Does Not Affect Keratinocyte Growth Inhibition

Abstract

We performed this study to determine the relationship between activation of nuclear factor (NF)-κB and inhibition of keratinocyte growth by anthralin, which not only might be useful for a better understanding of the role of NF-κB in the pathogenesis of psoriasis, but also indicate whether the inflammatory reaction induced by anthralin is inseparable from its antipsoriatic activity. The involvement of NF-κB was assessed using the antipsoriatic drugs leflunomide and triptolide (T₀) as effectors, since they can inhibit NF-κB activation induced by anthralin. The results showed that the inhibition of keratinocyte growth by anthralin was not related to the activation of NF-κB. Using sodium salicylate, a known NF-κB inhibitor, further confirmed this conclusion. Thus it might be possible to inhibit the inflammatory response induced by anthralin via repression of NF-κB activation. We found that leflunomide or T₀ could significantly inhibit the mRNA overexpression of interleukin-8 and intercellular adhesion molecule-1 in keratinocytes induced by anthralin. Taken together, our data indicate that the growth inhibition of anthralin is related to the NF-κB-independent signaling pathway, and that leflunomide or T₀ could control proinflammatory cytokine expression induced by anthralin via inhibiting the activation of NF-κB.