title: Zinc finger protein A20 is involved in the antipsoriatic effect of calcipotriol.
abstract: BACKGROUND
  Calcipotriol ameliorates psoriasis through inducing keratinocyte apoptosis and inhibiting nuclear factor kappa B (NF-κB) activation, while zinc finger protein A20 exhibits an anti-apoptotic effect on various types of cells.
  
  
  OBJECTIVE
  To understand the potential role of A20 in calcipotriol function.
  
  
  METHODS
  The A20 levels were evaluated in the psoriatic skins from both human patients and K14-vascular endothelial growth factor (VEGF) transgenic mice that received or did not receive topical calcipotriol treatment. The in vitro effect of calcipotriol on A20 expression and the downstream NF-κB pathway was studied using a model of human foreskin keratinocytes (HFKs) that were stimulated with psoriatic cytokines [M5, a cocktail of interleukin (IL)-1a, IL-17A, IL-22, Oncostatin M and tumour necrosis factor-α, each at 10 ng mL(-1) ].
  
  
  RESULTS
  A20 expression was enhanced in both psoriatic tissues and keratinocytes when compared with controls, but decreased on calcipotriol treatment. The transfection of A20 small interfering RNA (siRNA) improved cell differentiation, and inhibited psoriatic inflammation in a HFK model. Moreover, the nuclear expression of NF-κB p65 decreased on A20 downregulation in psoriatic tissues and keratinocytes. Interestingly, calcipotriol enhanced the binding of A20 to ring finger protein 114 (RNF114) and A20-binding inhibitor of NF-κB-1 (ABIN-1) in HFKs, two negative regulators of the NF-κB pathway.
  
  
  CONCLUSIONS
  Calcipotriol exhibits its antipsoriatic function through suppressing A20 expression and stabilizing negative regulators of the NF-κB pathway.
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Teng
authors.affiliation: Department of Medicine, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710004, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003872:Dermatitis / Q000378:metabolism; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism; D014162:Transfection; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016207:Cytokines; D003879:Dermatologic Agents; D016328:NF-kappa B; D034741:RNA, Small Interfering; C055085:calcipotriene; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D002117:Calcitriol