title: Serum amyloid A, an acute phase protein, stimulates proliferative and proinflammatory responses of keratinocytes.
abstract: OBJECTIVE
  Serum amyloid A (SAA), an acute phase protein, is highly expressed in psoriatic lesions but its function is not fully understood. The aim of this study was to explore its role in activation of keratinocytes.
  
  
  METHODS
  Real-time PCR and immunofluorescence were performed to examine SAA expression in imiquimod (IMQ)-induced psoriasis-like mice. In vivo function of SAA was examined by treating psoriasis-like mice with SAA neutralising antibody. Cell viability was monitored using the CCK-8 assay. Real-time PCR was performed to determine expression of genes associated with differentiation and inflammation. Ki67+percentage and immunological markers were analysed by flow cytometry. Involvement of formyl peptide receptor-like 1 (FPRL1) in SAA signal transduction was determined by RNA interference. Binding of SAA and FPRL1 was examined by co-immunoprecipitaion. Western blotting was conducted to assess phosphorylation of downstream signalling molecules.
  
  
  RESULTS
  SAA was highly expressed in skin lesions of IMQ-treated psoriasis-like mice and neutralising SAA attenuated epidermal hyperplasia and inflammation. SAA in vitro promoted keratinocyte proliferation and expression of immunological mediators, while inhibiting differentiation. Effects of SAA on keratinocyte proliferation and inflammation were mediated by FPRL1, as well as activation of the PI3K/Akt pathway.
  
  
  CONCLUSIONS
  These observations indicate that SAA/FPRL1 contributed to pathogenesis of psoriasis by promoting keratinocyte proliferation and inflammation, thus providing a potential therapeutic target for disease therapy.
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yu
authors.affiliation: Experimental Research Center, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Jiajing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Yangfeng
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000685:Serum Amyloid A Protein
keywords: imiquimod-induced psoriasis-like mouse; keratinocytes; psoriasis; serum amyloid A