Increased nitric oxide production by airway cells of sensitized and challenged IL-10 knockout mice.
The anti-inflammatory cytokine interleukin (IL)-10 suppresses inducible nitric oxide synthase (iNOS); therefore, NO production should increase in the absence of IL-10. Production of NO (as nitrite) by bronchoalveolar lavage cells of IL-10 knockout ((-/-)) mice was assessed after ovalbumin sensitization and airway challenge (S/C) and was compared with the IL-10-sufficient, wild-type (WT) C57Bl6. Eosinophil recruitment occurred in S/C WT and IL-10(-/-) mice, suggesting allergic airway inflammation. Alveolar macrophages (per g mouse) were unchanged (approximately 3x10(4) cells) with the exception of a doubling in the S/C IL-10(-/-) mice (approximately 6x10(4) cells, P<0.05). NO production (per million cells) was doubled in cells from S/C IL-10(-/-) (15.3 microM) mice compared with WT (7.6 microM, P<0.05). Inhibition of iNOS by L-N(5)-(1-iminoethyl)-ornithine reduced NO production in all S/C mice, confirming that the increase was a result of up-regulation of iNOS. We conclude that IL-10 is a critical cytokine regulating iNOS in murine airway cells and that its absence can lead to up-regulation of iNOS and development of allergic airway inflammation.
Ameredes
B T
BT
Asthma, Allergy, and Airway Research Center, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. ameredesbt@msx.upmc.edu
Zamora
R
R
Gibson
K F
KF
Billiar
T R
TR
Dixon-McCarthy
B
B
Watkins
S
S
Calhoun
W J
WJ
D000336:Aerosols; D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology; D007114:Immunization; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000276:immunology; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D000336:Aerosols; D015415:Biomarkers; D004791:Enzyme Inhibitors; D009573:Nitrites; D012333:RNA, Messenger; D016753:Interleukin-10; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D010047:Ovalbumin; D009952:Ornithine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse