title: Enhanced MCP-1 release by keloid CD14+ cells augments fibroblast proliferation: role of MCP-1 and Akt pathway in keloids.
abstract: Keloids are fibrous overgrowth induced by cutaneous injury. The pathogenesis of keloids is poorly understood, and no convincing animal model exists. Current hypotheses of the pathogenesis classify keloids as an entity of aberrant fibrosis. Hyperactivation of the MCP-1/CCR2 axis reportedly causes fibrosis in liver cirrhosis, atherosclerosis and lung fibrosis. Circulating CD14+ monocytes are precursors of circulating fibrocytes and contribute to fibrogenesis by a MCP-1/CCR2-dependent loop. As there is an increase in monocyte lineages in keloids, the aim of this study is to determine whether peripheral CD14+ monocytes in keloid patients trigger fibroblast proliferation through MCP-1. Expressions of MCP-1 and its receptor CCR2 in keloid lesions were measured by immunohistochemistry and real-time PCR. The results revealed an increase in MCP-1 and CCR2 in the keloid tissues. Co-culture of keloid CD14+ cells and normal fibroblasts enhanced fibroblast proliferation and a parallel increase in extracellular MCP-1. We further found that MCP-1 modest enhanced fibroblast proliferation via Akt activation. Blockade of either MCP-1 or Akt signaling suppressed the mediation of fibroblast proliferation by CD14+ cells from patients. These results demonstrated that enhanced MCP-1 release by keloid CD14+ cells augments fibroblast proliferation via Akt pathway in keloids. We concluded that enhanced MCP-1 release by keloid CD14+ cells augments fibroblast proliferation, which might initiate keloid development.
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Liao
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
authors.forename: Jack L
authors.initials: JL
authors.lastname: Arbiser
authors.forename: Chein-Hui
authors.initials: CH
authors.lastname: Hong
authors.forename: Baskaran
authors.initials: B
authors.lastname: Govindarajan
authors.forename: Chih-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Shan
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Lin
authors.forename: Gwo-Shing
authors.initials: GS
authors.lastname: Chen
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054390:Receptors, CCR2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D018950:Lipopolysaccharide Receptors; D054390:Receptors, CCR2; D051057:Proto-Oncogene Proteins c-akt