title: Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.
abstract: Systemic sclerosis (SSc) is frequently associated with interstitial lung disease (ILD) often leading to lung fibrosis. In this study we investigated whether matrix metalloproteinase 9 (MMP-9) and its natural inhibitor; the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), would be associated with remodelling in ILD in SSc. Levels of total MMP-9, pro-MMP-9 and TIMP-1 were measured in bronchoalveolar lavage (BAL) fluid from nine SSc patients with ILD, seven SSc patients without ILD and 16 age- and sex-matched healthy controls. Total MMP-9 and pro-MMP-9 levels were significantly elevated in SSc patients with ILD, compared to levels in SSc patients without ILD and healthy controls. In SSc patients with ILD calculated active MMP-9 levels were significantly higher than in SSc patients without ILD and tended to be higher than in healthy controls. TIMP-1 levels were elevated in both patient groups compared to healthy controls. Total-, pro- and active MMP-9 levels as well as pro-MMP-TIMP-1 and active MMP-9/TIMP-1 ratios were inversely associated with total lung capacity. The present study suggests that MMP-9 plays a pathophysiological role in the remodelling in ILD and lung fibrosis associated with SSc, and may represent a new therapeutic target in this condition.
authors.affiliation: Department of Rheumatology, University Hospital of Umeå, Umeå, Sweden.
authors.forename: Grethe Neumann
authors.initials: GN
authors.lastname: Andersen
authors.forename: Kenneth
authors.initials: K
authors.lastname: Nilsson
authors.forename: Jamshid
authors.initials: J
authors.lastname: Pourazar
authors.forename: Tillie-Louise
authors.initials: TL
authors.lastname: Hackett
authors.forename: Elsadig
authors.initials: E
authors.lastname: Kazzam
authors.forename: Anders
authors.initials: A
authors.lastname: Blomberg
authors.forename: Anders
authors.initials: A
authors.lastname: Waldenström
authors.forename: Jane
authors.initials: J
authors.lastname: Warner
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
authors.forename: Lucia
authors.initials: L
authors.lastname: Mincheva-Nilsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Sandström
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D017563:Lung Diseases, Interstitial / Q000201:enzymology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils; D012129:Respiratory Function Tests / Q000379:methods; D012595:Scleroderma, Systemic / Q000201:enzymology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9