title: The chemokine receptor CCR3 participates in tissue remodeling during atopic skin inflammation.
abstract: BACKGROUND
  Recent studies provided insights into the recruitment and activation pathways of leukocytes in atopic dermatitis, however, the underlying mechanisms of tissue remodeling in atopic skin inflammation remain elusive.
  
  
  OBJECTIVE
  To identify chemokine-mediated communication pathways regulating tissue remodeling during atopic skin inflammation.
  
  
  METHODS
  Analysis of the chemokine receptor repertoire of human dermal fibroblasts using flow cytometry and immunofluorescence. Quantitative real-time polymerase chain reaction and immunohistochemical analyses of chemokine expression in atopic vs. non-atopic skin inflammation. Investigation of the function of chemokine receptor CCR3 on human dermal fibroblasts through determining intracellular Ca(2+) mobilization, cell proliferation, migration, and repair capacity.
  
  
  RESULTS
  Analyses on human dermal fibroblasts showed abundant expression of the chemokine receptor CCR3 in vitro and in vivo. Among its corresponding ligands (CCL5, CCL8, CCL11, CCL24 and CCL26) CCL26 demonstrated a significant and specific up-regulation in atopic when compared to psoriatic skin inflammation. In vivo, epidermal keratinocytes showed most abundant CCL26 protein expression in lesional atopic skin. In structural cells of the skin, TH2-cytokines such as IL-4 and IL-13 were dominant inducers of CCL26 expression. In dermal fibroblasts, CCL26 induced CCR3 signaling resulting in intracellular Ca(2+) mobilization, as well as enhanced fibroblast migration and repair capacity, but no proliferation.
  
  
  CONCLUSIONS
  Taken together, findings of the present study suggest that chemokine-driven communication pathways from the epidermis to the dermis may modulate tissue remodeling in atopic skin inflammation.
authors.affiliation: Department of Dermatology, University Hospital, Duesseldorf, Germany.
authors.forename: Krisztian
authors.initials: K
authors.lastname: Gaspar
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kukova
authors.forename: Erich
authors.initials: E
authors.lastname: Bunemann
authors.forename: Bettina Alexandra
authors.initials: BA
authors.lastname: Buhren
authors.forename: Eniko
authors.initials: E
authors.lastname: Sonkoly
authors.forename: Attila Gabor
authors.initials: AG
authors.lastname: Szollosi
authors.forename: Anja
authors.initials: A
authors.lastname: Muller
authors.forename: Terhi
authors.initials: T
authors.lastname: Savinko
authors.forename: Antti I
authors.initials: AI
authors.lastname: Lauerma
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Lajos
authors.initials: L
authors.lastname: Kemeny
authors.forename: Marie-Caroline
authors.initials: MC
authors.lastname: Dieu-Nosjean
authors.forename: Sonja
authors.initials: S
authors.lastname: Stander
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Albert
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Andrea
authors.initials: A
authors.lastname: Szegedi
authors.forename: Bernhard
authors.initials: B
authors.lastname: Homey
mesh_terms: D020013:Calcium Signaling; D016022:Case-Control Studies; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology; D008024:Ligands; D054397:Receptors, CCR3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: C120429:CCL26 protein, human; C515350:CCR3 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; C508598:IL4 protein, human; D018836:Inflammation Mediators; D018793:Interleukin-13; D008024:Ligands; D054397:Receptors, CCR3; D015847:Interleukin-4