title: A comparison of the effects of topical treatment of calcipotriol, camptothecin, clobetasol and tazarotene on an imiquimod-induced psoriasis-like mouse model.
abstract: The interleukin-23/interleukin 17A (IL-23/IL-17A) cytokine axis plays a critical role in the pathogenesis of psoriasis. In this study, we report the effects of topical calcipotriol, camptothecin, clobetasol and tazarotene on the treatment of imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which is dependent on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in the BALB/c mouse ear were significantly inhibited following clobetasol treatment but not calcipotriol, camptothecin or tazarotene treatments. Real-time polymerase chain reaction showed that the mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α in ear skin were significantly decreased by clobetasol. In addition, we observed that calcipotriol, camptothecin and tazarotene failed to show any inhibitory effects on the IL-23/IL-17A/IL-22 axis. We also found that clobetasol treatment inhibited the proliferation of γδ T cells and C-C chemokine receptor type 6 (CCR6) expression induced by IMQ. Calcipotriol, camptothecin and tazarotene not only failed to inhibit this proliferation but also enhanced retinoic acid-related orphan receptor γ (RORγ) expression in IMQ-induced psoriasis-like inflammation. In conclusion, we suggest that clobetasol induces the relief of IMQ-induced psoriasis-like inflammation in a mouse model but that calcipotriol, camptothecin and tazarotene cannot. Therefore, we suggest that more in-depth studies on pharmacological effects of tazarotene, camptothecin and calcipotriol should be carried out.
authors.affiliation: Department of Pharmacy, Changhai Hospital, the Second Military Medical University , Shanghai , China and.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Dou
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jinhong
authors.initials: J
authors.lastname: Hu
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000287:Administration, Topical; D000634:Aminoquinolines / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology*; D002990:Clobetasol / Q000494:pharmacology*; D003879:Dermatologic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D000077271:Imiquimod; D051379:Mice; D008807:Mice, Inbred BALB C; D009539:Nicotinic Acids / Q000494:pharmacology*; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology*; D012176:Retinoids
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000893:Anti-Inflammatory Agents; D002117:Calcitriol; D002166:Camptothecin; D002990:Clobetasol; D003879:Dermatologic Agents; D000077271:Imiquimod; D009539:Nicotinic Acids; D059004:Topoisomerase I Inhibitors; C055085:calcipotriene; C086827:tazarotene; D012176:Retinoids