title: Elevated levels of platelet derived growth factor and transforming growth factor-beta 1 in bronchoalveolar lavage fluid from patients with scleroderma.
abstract: OBJECTIVE
  Systemic sclerosis (scleroderma, SSc) frequently affects the lungs, and interstitial pulmonary fibrosis is one of its major complications. The pathophysiology of SSc lung disease s poorly understood, but recent studies document an inflammatory process resembling that of idiopathic pulmonary fibrosis with increased numbers of activated alveolar macrophages and granulocytes in bronchoalveolar lavage (BAL) fluid). We determined levels of 2 potentially important mediators of fibroproliferative repair in BAL fluid from patients with SSc.
  
  
  METHODS
  Using Western blot and ELISA techniques we measured levels of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta in BAL fluid from patients with SSc and healthy controls. The mitogenic effect of these cytokines on SSc lung myofibroblasts was determined by [3H]thymidine incorporation.
  
  
  RESULTS
  SSc BAL fluid contains significantly elevated levels of PDGF-AA and PDGF-BB. Where TGF-beta 1 was significantly elevated in SSc lavage fluid, the amount of TGF-beta 2 was significantly less than that observed in normal lavage fluid. Myofibroblasts cultured from SSc lavage fluid exhibited enhanced [3H]thymidine incorporation upon exposure to the growth factors present in SSc BAL fluid: PDGF and TGF-beta 1. SSc lung myofibroblasts pretreated with TGF-beta 1 exhibited an enhanced mitogenic effect upon stimulation by PDGF, due in part to the induction of the PDGF alpha receptor.
  
  
  CONCLUSIONS
  Our studies support a role for PDGF and TGF-beta 1 in the pathogenesis of SSc lung disease.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charlestown 29425, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ludwicka
authors.forename: T
authors.initials: T
authors.lastname: Ohba
authors.forename: M
authors.initials: M
authors.lastname: Trojanowska
authors.forename: A
authors.initials: A
authors.lastname: Yamakage
authors.forename: C
authors.initials: C
authors.lastname: Strange
authors.forename: E A
authors.initials: EA
authors.lastname: Smith
authors.forename: E C
authors.initials: EC
authors.lastname: Leroy
authors.forename: S
authors.initials: S
authors.lastname: Sutherland
authors.forename: R M
authors.initials: RM
authors.lastname: Silver
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002455:Cell Division; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007536:Isomerism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor