Acrolein inhalation suppresses lipopolysaccharide-induced inflammatory cytokine production but does not affect acute airways neutrophilia.
Acrolein is a reactive unsaturated aldehyde that is produced during endogenous oxidative processes and is a major bioactive component of environmental pollutants such as cigarette smoke. Because in vitro studies demonstrate that acrolein can inhibit neutrophil apoptosis, we evaluated the effects of in vivo acrolein exposure on acute lung inflammation induced by LPS. Male C57BL/6J mice received 300 microg/kg intratracheal LPS and were exposed to acrolein (5 parts per million, 6 h/day), either before or after LPS challenge. Exposure to acrolein either before or after LPS challenge did not significantly affect the overall extent of LPS-induced lung inflammation, or the duration of the inflammatory response, as observed from recovered lung lavage leukocytes and histology. However, exposure to acrolein after LPS instillation markedly diminished the LPS-induced production of several inflammatory cytokines, specifically TNF-alpha, IL-12, and the Th1 cytokine IFN-gamma, which was associated with reduction in NF-kappaB activation. Our data demonstrate that acrolein exposure suppresses LPS-induced Th1 cytokine responses without affecting acute neutrophilia. Disruption of cytokine signaling by acrolein may represent a mechanism by which smoking contributes to chronic disease in chronic obstructive pulmonary disease and asthma.
Department of Pathology, Vermont Lung Center, College of Medicine, University of Vermont, Burlington, VT 05405, USA.
David Itiro
DI
Kasahara
Matthew E
ME
Poynter
Ziryan
Z
Othman
David
D
Hemenway
Albert
A
van der Vliet
D000171:Acrolein / Q000008:administration & dosage* / Q000494:pharmacology*; D000208:Acute Disease; D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000171:Acrolein; D048031:JNK Mitogen-Activated Protein Kinases