title: The CKLF1-C19 peptide attenuates allergic lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma.
abstract: BACKGROUND
  Human chemokine-like factor 1 (CKLF1) is a functional ligand for human CCR4, which is highly expressed on Th2 lymphocytes and plays an important role in the pathogenesis of asthma. The expression and function of CKLF1 are associated with asthma. The CKLF1 C-terminal peptides C19 and C27 also interact with human CCR4. Albeit with weaker chemotactic activity, C19 can inhibit chemotaxis induced by both CKLF1 and CCL17. Here, we explore whether C19 can act as an antagonist in the development of asthma.
  
  
  METHODS
  A mouse model of asthma and in vitro and in vivo chemotaxis assays were used.
  
  
  RESULTS
  Using a mouse model of asthma, we demonstrate here that C19 reduces airway eosinophilia, lung inflammation and airway hyperresponsiveness; in contrast, C27 has little effect on these parameters. The inhibitory effects of C19 on CCR4-mediated chemotaxis could be observed in human Th2 lymphocytes and in the splenocytes from ovalbumin-sensitized mice. Furthermore, we show that C19 can inhibit CCL11-induced chemotaxis of mouse eosinophils and human CCR3-transfected or mouse Ccr3-transfected HEK293 cells. In vivo chemotaxis assays revealed that C19 and C27 can reduce CCL11-mediated recruitment of eosinophils into the peritoneal cavity and that this inhibitory effect is stronger for C19 than for C27.
  
  
  CONCLUSIONS
  Thus, C19 can attenuate airway eosinophilia and lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma. Given its ability to inhibit human CCR3- and CCR4-meditated chemotaxis, C19 has great therapeutic potential for use in the treatment and control of allergic asthma.
authors.affiliation: Department of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, #38 Xueyuan Road, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: H
authors.initials: H
authors.lastname: Qi
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D016535:Bronchial Hyperreactivity; D002464:Cell Migration Inhibition; D018925:Chemokines / Q000494:pharmacology* / Q000627:therapeutic use; D002633:Chemotaxis / Q000187:drug effects*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D054398:Receptors, CCR4 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C432676:CKLF protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D010446:Peptide Fragments; D054397:Receptors, CCR3; D054398:Receptors, CCR4