Inhibition of the nuclear factor-kappaB signaling pathway by leflunomide or triptolide also inhibits the anthralin-induced inflammatory response but does not affect keratinocyte growth inhibition.
We performed this study to determine the relationship between activation of nuclear factor (NF)-kappaB and inhibition of keratinocyte growth by anthralin, which not only might be useful for a better understanding of the role of NF-kappaB 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-kappaB was assessed using the antipsoriatic drugs leflunomide and triptolide (T0) as effectors, since they can inhibit NF-kappaB activation induced by anthralin. The results showed that the inhibition of keratinocyte growth by anthralin was not related to the activation of NF-kappaB. Using sodium salicylate, a known NF-kappaB inhibitor, further confirmed this conclusion. Thus it might be possible to inhibit the inflammatory response induced by anthralin via repression of NF-kappaB 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-kappaB-independent signaling pathway, and that leflunomide or T0 could control proinflammatory cytokine expression induced by anthralin via inhibiting the activation of NF-kappaB.
Feng
Hua
H
Department of Materia Medica, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
Li
Xin-Yu
XY
Zheng
Jia-Run
JR
Gao
Ji-Wei
JW
Xu
Lan-Fang
LF
Tang
Mei-Yu
MY
D000875:Anthralin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects*; D000077339:Leflunomide; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016209:Interleukin-8; D007555:Isoxazoles; D016328:NF-kappa B; D010616:Phenanthrenes; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D018799:Intercellular Adhesion Molecule-1; C001899:triptolide; C022616:thiazolyl blue; D000077339:Leflunomide; D000875:Anthralin