title: Lipoxin A4 inhibits proliferation and inflammatory cytokine/chemokine production of human epidermal keratinocytes associated with the ERK1/2 and NF-κB pathways.
abstract: BACKGROUND
  Current in vitro studies show that lipoxin A4 (LXA4) has multiple biological functions including inhibiting cell proliferation and inflammatory cytokine production. Our previous studies showed LXA4 could inhibit the expression of IL-6 and IL-8 in normal human epidermal keratinocytes (NHEKs). However, more specific effects including regulation of cell proliferation and anti-inflammatory mechanisms of LXA4 in NHEKs have not been previously studied.
  
  
  OBJECTIVE
  We proposed to investigate the effects of LXA4 on cell proliferation and inflammatory cytokine/chemokine production in NHEKs, and the possible molecular mechanisms of cell cycle and anti-inflammatory signal transduction pathway.
  
  
  METHODS
  NHEKs were stimulated with LPS, with or without preincubation with LXA4. Cell proliferation and cell cycle of NHEKs were examined by WST-8, CFSE assay and DNA staining, respectively. The mRNA and protein levels of inflammatory cytokines were quantified by real-time quantitative PCR and ELISA. The expressions of signaling proteins cyclin D1, P16INK4A, ERK1/2 and NF-κB-p65 were analyzed using Western blotting.
  
  
  RESULTS
  Cell proliferation and inflammatory cytokine/chemokine production of NHEKs were suppressed by LXA4, which caused G0/G1 phase cell cycle arrest in NHEKs. The expression of cyclin D1 was down-regulated by LXA4, contrary to the results of P16INK4A. The ERK1/2 phosphorylation and NF-κB-p65 nuclear translocation of NHEKs were both suppressed by LXA4.
  
  
  CONCLUSIONS
  Cell growth and inflammatory cytokine/chemokine production of NHEKs were inhibited by LXA4, and the inhibitory effects might be associated with the mechanisms of cyclin D1/P16INK4A, ERK1/2 and NF-κB signal transduction pathway.
authors.affiliation: Department of Dermatology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alashkar
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Zhong
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Meng-Wen
authors.initials: MW
authors.lastname: He
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: arztfeng@126.com.
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Feng
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: hongxiangchen@hotmail.com.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Chen
mesh_terms: D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D019938:Cyclin D1 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis*; D000078404:Epidermal Cells; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D044045:Lipoxins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018925:Chemokines; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016207:Cytokines; D008070:Lipopolysaccharides; D044045:Lipoxins; D016328:NF-kappa B; C040527:lipoxin A4; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cell cycle; Cell proliferation; Inflammation; Keratinocyte; Lipoxin A4