title: Interleukin-4 and interleukin-13 enhance human bronchial smooth muscle cell proliferation.
abstract: BACKGROUND
  T(H)2 inflammation and bronchial smooth muscle cell (BSMC) hyperplasia are characteristic features of asthma, but whether these phenomena are linked remains unknown. This study aims to define the effect of the T(H)2 cytokines IL-4 and IL-13 on human BSMC proliferation when administered alone or in combination with the fibroblast growth factor 2 (FGF2) growth factor. In addition, the effects of the proinflammatory mediators TNFalpha and IL-1 beta and the involvement of members of the well-known family of platelet-derived growth factor (PDGF) mitogens were tested.
  
  
  METHODS
  BSMC proliferation was measured by crystal violet staining and PDGF and PDGF receptor (PDGFR) expression were determined by RT-PCR, immunocytochemistry, ELISA, flow cytometry and dot plot analysis.
  
  
  RESULTS
  Neither IL-4 nor IL-13 alone induced BSMC proliferation, despite both being potent inducers of PDGF-CC. However, following a pretreatment with FGF2, which increased PDGFR alpha chain expression, both IL-4 and IL-13 increased FGF2-induced BSMC proliferation in a time- and concentration-dependent manner. TNFalpha and IL-1 beta did not affect basal or FGF2-induced BSMC proliferation, but both proinflammatory mediators enhanced the proliferative synergism between FGF2 and the T(H)2 cytokines.
  
  
  CONCLUSIONS
  IL-4 and IL-13 potently induce FGF2-primed BSMC proliferation via an autocrine loop involving PDGFRalpha and PDGF-CC, and this proliferative synergism is amplified by proinflammatory cytokines.
authors.affiliation: Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: Ynuk
authors.initials: Y
authors.lastname: Bossé
authors.forename: Charles
authors.initials: C
authors.lastname: Thompson
authors.forename: Karine
authors.initials: K
authors.lastname: Audette
authors.forename: Jana
authors.initials: J
authors.lastname: Stankova
authors.forename: Marek
authors.initials: M
authors.lastname: Rola-Pleszczynski
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D001980:Bronchi / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D006965:Hyperplasia / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D018793:Interleukin-13 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D018793:Interleukin-13; D016222:Fibroblast Growth Factor 2; D015847:Interleukin-4