Inhibitory role of eosinophils on cell surface plasmin generation by bronchial epithelial cells: inhibitory effects of transforming growth factor beta.
Eosinophilic bronchitis is an essential component of bronchial asthma, and eosinophils play an important role. We studied the effect of eosinophils on cell surface plasmin generation by bronchial epithelial cells, because plasmin is thought to be involved in bronchial tissue repair/remodeling by means of fibrinolysis and the activation of proteases such as matrix metalloproteases. Plasmin was generated from exogenous plasminogen on the cell surface of cultured bronchial epithelial cells, NCI-H292. Transforming growth factor beta (TGF-beta) treatment resulted in reduced cell surface plasmin generation and a large increase in plasminogen activator inhibitor-type 1 (PAI-1) antigen production in NCI-H292 cells, whereas no conspicuous effects were observed with IL-1 beta and TNF alpha treatment (regulators in pulmonary epithelial cells). On the other hand, this cell surface plasmin generation was reduced by co-incubation with Eol-1, an eosinophil cell line. The addition of TGF-beta antisense and anti-TGF-beta antibodies attenuated this adverse effect of Eol-1 cell co-incubation. These data suggest that eosinophils play an inhibitory role on cell surface plasmin generation by bronchial epithelial cells by means of the up-regulation of PAI-1 expression induced by TGF-beta. Therefore, the accumulation of eosinophils in bronchial walls is thought to be involved in bronchial tissue repair/remodeling in asthma through this protease network.
Hara
K
K
Department of Medicine II, Niigata University School of Medicine, Niigata, Japan.
Hasegawa
T
T
Ooi
H
H
Koya
T
T
Tanabe
Y
Y
Tsukada
H
H
Igarashi
K
K
Suzuki
E
E
Arakawa
M
M
Gejyo
F
F
D001249:Asthma / Q000503:physiopathology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000502:physiology*; D004847:Epithelial Cells / Q000473:pathology*; D005341:Fibrinolysin / Q000096:biosynthesis*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation
D016376:Oligonucleotides, Antisense; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D005341:Fibrinolysin