title: Mechanical strain increases cytokine and chemokine production in bronchial fibroblasts from asthmatic patients.
abstract: BACKGROUND
  Mechanical strain and cytokine stimulation are two important mechanisms leading to airway remodeling in asthma. The effect of mechanical strain on cytokine secretion in airway fibroblasts is not known. The aim of this study was to determine whether bronchial and nasal fibroblasts differentially alter cytokine secretion in response to mechanical strain.
  
  
  METHODS
  We measured secretion of the pro-fibrotic cytokine, interleukin-6 (IL-6), and the pro-inflammatory cytokines, IL-8 and monocyte chemotactic protein 1, before and after mechanical strain in bronchial fibroblasts obtained from asthmatic patients [asthmatic bronchial fibroblasts (BAF)] and normal volunteers [normal bronchial fibroblasts (BNF)], and in nasal fibroblasts (NF) obtained from nasal polyps. Cells were grown on flexible membranes and a mechanical strain of 30% amplitude, 1 Hz frequency was applied for 3, 6 and 24 h. Control cells were unstrained. IL-6, IL-8 and monocyte chemotactic protein 1 was measured after 24 h strain using enzyme-linked immunoassay; mRNA was measured by real time polymerase chain reaction. We also measured mRNA for versican, a matrix proteoglycan, known to be upregulated in the asthmatic airway wall.
  
  
  RESULTS
  In unstrained conditions, no differences in cytokine secretion were observed. After 24 h strain, BAF secreted more IL-6 than BNF. Mechanical strain increased IL-8 mRNA in BAF, BNF and NF; and IL-6 and versican mRNA, in BAF, only.
  
  
  CONCLUSIONS
  Cytokine responses to mechanical strain varied in different airway fibroblast populations, and depended on the site of origin, and the underlying inflammatory state. Strain resulted in IL-6 upregulation and increased message for extracellular matrix protein in bronchial fibroblasts from asthmatic patients only, and may reflect these patients' propensity for airway remodeling.
authors.affiliation: Meakins-Christie Laboratories, McGill University Hospital Center, Montreal, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Le Bellego
authors.forename: H
authors.initials: H
authors.lastname: Perera
authors.forename: S
authors.initials: S
authors.lastname: Plante
authors.forename: J
authors.initials: J
authors.lastname: Chakir
authors.forename: Q
authors.initials: Q
authors.lastname: Hamid
authors.forename: M S
authors.initials: MS
authors.lastname: Ludwig
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology / Q000473:pathology*; D001696:Biomechanical Phenomena / Q000235:genetics*; D001980:Bronchi / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D015850:Interleukin-6