Bronchoalveolar matrix metalloproteinase 9 relates to restrictive lung function impairment in systemic sclerosis.
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.
Andersen
Grethe Neumann
GN
Department of Rheumatology, University Hospital of Umeå, Umeå, Sweden.
Nilsson
Kenneth
K
Pourazar
Jamshid
J
Hackett
Tillie-Louise
TL
Kazzam
Elsadig
E
Blomberg
Anders
A
Waldenström
Anders
A
Warner
Jane
J
Rantapää-Dahlqvist
Solbritt
S
Mincheva-Nilsson
Lucia
L
Sandström
Thomas
T
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
D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9