title: Expression and regulation of CCL15 by human airway smooth muscle cells.
abstract: BACKGROUND
  Structural cells are an important reservoir of chemokines that coordinate the influx of various immune cells to the lungs of asthmatics. Airway smooth muscle cells (ASMC) are an important source of these chemokines. CCL15 is a recently described chemo-attractant for neutrophils, eosinophils, monocytes and lymphocytes.
  
  
  OBJECTIVE
  To determine the production and the regulation of CCL15 by ASMC and to investigate its production in asthmatic airways.
  
  
  METHODS
  Human ASMC were obtained from main bronchial airway segments of patients with mild, moderate and severe asthma. To induce chemokine production, cells were incubated with IL-4, IL-13, TNF-α or IFN-γ in presence or absence of dexamethasone, mithramycin A (SP-1 inhibitor) or the IKK-2 inhibitor, AS602868. CCL15 mRNA expression was evaluated by real-time PCR. Immunoreactive CCL15 was detected by immuno-fluorescence and CCL15 protein concentration in the supernatant was measured using ELISA.
  
  
  RESULTS
  CCL15 is constitutively expressed in human ASMC and is strongly up-regulated by TNF-α. This up-regulation is inhibited by dexamethasone, mithramycin A and AS602868. TNF-α-induced CCL15 levels can be synergistically enhanced by the presence of IFN-γ, at both the transcriptional and translation level. This synergism is NF-κB-dependent. Asthmatic biopsies demonstrated higher expression of CCL15 compared with non-asthmatic controls.
  
  
  CONCLUSIONS
  Our results show that ASMC are a potent source of CCL15 in the airways and may directly participate in the recruitment of inflammatory cells to asthmatic airways. Targeting the production of CCL15 by ASMC might reduce the inflammatory response within the airways of asthmatic patients.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Joubert
authors.forename: S
authors.initials: S
authors.lastname: Lajoie-Kadoch
authors.forename: V
authors.initials: V
authors.lastname: Wellemans
authors.forename: S
authors.initials: S
authors.lastname: Létuvé
authors.forename: M K
authors.initials: MK
authors.lastname: Tulic
authors.forename: A J
authors.initials: AJ
authors.lastname: Halayko
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000503:physiopathology*; D001706:Biopsy; D001980:Bronchi / Q000166:cytology*; D019742:Chemokines, CC / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C108814:CCL15 protein, human; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma