Inhibition of inducible nitric oxide synthase expression by interleukin-4 and interleukin-13 in human lung epithelial cells.
Nitric oxide produced by the inducible enzyme, nitric oxide synthase (iNOS), is implicated in immunological and inflammatory processes. We determined the effects of T-helper (Th)2-derived cytokines on the induction of iNOS from an epithelial A549 cell line and human airway epithelial cells stimulated by a mixture of interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Interleukin-4 (IL-4) and interleukin-13 (IL-13) but not interleukin-10 (IL-10) inhibited both iNOS mRNA expression and nitrite release in A549 cells. On human airway epithelial cells, IL-4 and IL-13 reduced iNOS mRNA expression. Dexamethasone also inhibited both iNOS expression and nitrite release. Th2 cytokines, IL-4 and IL-13, inhibit iNOS upregulation by Th1 cytokines, indicating an important reciprocal role of Th1 and Th2 T-cell subsets on lung epithelial cells.
Berkman
N
N
Department of Thoracic Medicine, National Heart & Lung Institute, Imperial College of Science, Technology & Medicine, London, UK.
Robichaud
A
A
Robbins
R A
RA
Roesems
G
G
Haddad
E B
EB
Barnes
P J
PJ
Chung
K F
KF
D015152:Blotting, Northern; D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004848:Epithelium / Q000201:enzymology / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008168:Lung / Q000201:enzymology / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
D016207:Cytokines; D018793:Interleukin-13; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015847:Interleukin-4; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase