Inducible nitric oxide synthase expression and nuclear factor-kappaB activation in alveolar type II cells in lung injury.
Alveolar type II cells (type II cells) play a crucial role in the progression and repair of lung inflammation and injury. We investigated whether inducible nitric oxide synthase (iNOS) was expressed and nuclear factor-kappaB (NF-kappaB) was activated in type II cells in lung injury. After injecting lipopolysaccharide (LPS) or saline in the rat, the lungs were excised and type II cells were isolated. iNOS and its mRNA were expressed both in lung tissue and isolated type II cells in response to LPS. The lungs from saline-treated rats showed only minimal expression of iNOS. Electrophoretic mobility shift assay revealed that expression of NF-kappaB in the nuclear extracts was augmented by LPS, and p5O/NFkappaB was expressed in type II cells in LPS-treated rats. Intraperitoneal dexamethasone almost completely inhibited the iNOS expression and attenuated the activation of NF-kappaB in the LPS-treated lung. These findings suggest that type II cells can be a source of NO production in lung injury,and that the effects of corticosteroids may be in part through inhibition of both iNOS expression and NF-kappaB activation.
Toga
H
H
Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan. toga-h@kanazawa-med.ac.jp
Tobe
T
T
Ueda
Y
Y
Yang
G H
GH
Osanai
K
K
Ishigaki
M
M
Okazaki
H
H
Katsuda
S
S
Takahashi
K
K
Ohya
N
N
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011650:Pulmonary Alveoli / Q000166:cytology / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat