Constitutive expressions of type I NOS in human airway smooth muscle cells: evidence for an antiproliferative role.
In airway diseases, smooth muscle cells can proliferate at exaggerated rates; thus, the identification of endogenous pathways that limit proliferative responses is important. Here we show that human airway smooth muscle express type I nitric oxide synthase (NOS), which results in inhibition of DNA synthesis and cell proliferation. In addition, superoxide dismutase (SOD), a cell-permeable mimetic that increases the biological half-life and therefore enhances the biological activity of endogenously released nitric oxide (NO), or NO-releasing drugs also greatly reduce DNA synthesis and cell proliferation. Observations in this study have important clinical implications: 1) NOS inhibition may exacerbate airway disease and 2) inhaled SOD/mimetics or NO/nitrovasodilators may be therapies for the treatment of asthma or chronic obliterative pulmonary disease.
Patel
H J
HJ
Department of Thoracic Medicine and Cardiothoracic Surgery, Imperial College School of Medicine at the National Heart and Lung Institute, London, SW3 6LY, UK.
Belvisi
M G
MG
Donnelly
L E
LE
Yacoub
M H
MH
Chung
K F
KF
Mitchell
J A
JA
D000293:Adolescent; D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000201:enzymology*
D006131:Growth Inhibitors; C093285:NOC 18; D020030:Nitric Oxide Donors; D009573:Nitrites; D009603:Nitroso Compounds; D009569:Nitric Oxide; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester