title: Dermokine inhibits ELR(+)CXC chemokine expression and delays early skin wound healing.
abstract: BACKGROUND
  Dermokine-β is abundant in stratified epithelia and in differentiating keratinocytes in culture. We have recently shown that treatment of keratinocytes with dermokine-β attenuates phosphorylation of extracellular signal-regulated kinase, however, the roles of dermokine-β in vivo remain unknown.
  
  
  OBJECTIVE
  Dermokine-β is overexpressed in marginal keratinocytes during wound healing. This study was conducted to investigate the roles of dermokine-β in the wound healing process.
  
  
  METHODS
  Recombinant human dermokine-β or its active peptide was topically applied to excisional wounds in mice and the relative wound area was calculated. Histological and chemokine expression analyses in wounds were also performed. The chemokine expression levels as well as the chemotactic activity of dermokine-β in cultured keratinocytes were determined.
  
  
  RESULTS
  Topical application of recombinant dermokine-β as well as its carboxy-terminal domain peptide inhibited mouse wound healing at an early phase, reduced infiltration of neutrophils and macrophages into the wounds, inhibited angiogenesis, and decreased the number of myofibroblasts in the wounds. Treatment with dermokine-β augmented IL-10 expression, but attenuated expression of transforming growth factor-β and tumor necrosis factor-α. In addition, application of dermokine-β to skin wounds reduced the expression of CXCL1 and CXCL5, both of which are chemoattractant for neutrophils into wounds. Both dermokine-β and its active peptide decreased the expression of CXCL1, CXCL6, and CXCL8 in cultured human keratinocytes. Treatment of human keratinocytes with dermokine-β inhibited neutrophil chemotaxis.
  
  
  CONCLUSIONS
  These results suggest that dermokine-β delays early cutaneous wound healing in part by inhibiting expression of CXC chemokines containing the ERL-sequence motif.
authors: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan. minoruha@derma.m.kanazawa-u.ac.jp
authors: Minoru
authors: M
authors: Hasegawa
authors: Kiyoshi
authors: K
authors: Higashi
authors: Takashi
authors: T
authors: Matsushita
authors: Yasuhito
authors: Y
authors: Hamaguchi
authors: Koichi
authors: K
authors: Saito
authors: Manabu
authors: M
authors: Fujimoto
authors: Kazuhiko
authors: K
authors: Takehara
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics; D054427:Chemokine CXCL6 / Q000235:genetics; D002633:Chemotaxis / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: C475829:CXCL1 protein, human; C515503:CXCL6 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D054427:Chemokine CXCL6; C495568:DMKN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D011506:Proteins; D011994:Recombinant Proteins; C495569:dermokine protein, mouse