Quinacrine inhibits the epidermal dendritic cell migration initiating T cell-mediated skin inflammation

✍ Scribed by Anton V. Gorbachev; Alexander V. Gasparian; Katerina V. Gurova; Andrei V. Gudkov; Robert L. Fairchild

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 331 KB
• Volume: 37
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200636708

✦ Synopsis

Abstract

Quinacrine (QC) is an anti‐inflammatory drug that has been used for the treatment of malaria and rheumatoid diseases. The mechanism(s) underlying the anti‐inflammatory activity of QC remains poorly understood. We recently reported the QC‐mediated inhibition of the NF‐κB pathway using an in vitro model. To test this potential mechanism in vivo, we used the contact hypersensitivity response (CHS) to chemical allergen sensitization and challenge in mice as a model of skin inflammation. The results indicated that QC treatment inhibited NF‐κB activation in the skin during allergen sensitization. This inhibition was reflected by decreased mRNA expression and protein production of the NF‐κB‐dependent cytokines TNF‐α and IL‐1β and the chemokine CCL21 in the skin. The decreases in these cytokines resulted in reduced migration of allergen‐presenting dendritic cells from the skin into skin‐draining lymph nodes and markedly decreased activation of effector CD8^+^ T cells for the CHS response to allergen challenge (inhibitory concentration 50% or IC~50~ was 55 mg/kg). These findings reveal a previously unrecognized mechanism of QC‐mediated inhibition of inflammation.