Differential NF-kappaB activation after intratracheal endotoxin.
We examined the relationship between nuclear factor (NF)-kappaB DNA binding activity, cytokine gene expression, and neutrophilic alveolitis in rats after intratracheal (IT) instillation of endotoxin [lipopolysaccharide (LPS)]. NF-kappaB activation in lung tissue mirrored neutrophilic alveolitis after IT LPS instillation, with NF-kappaB activation and neutrophilic influx beginning 2 h after IT LPS doses of 0.01 mg/kg or greater. In lung lavage fluid cells, however, transient NF-kappaB activation was present in alveolar macrophages by 15 min after IT LPS instillation, followed by a second peak of NF-kappaB activation corresponding to the onset on neutrophilic alveolitis. For cytokines thought to be NF-kappaB dependent, two different patterns of mRNA expression were found. Interleukin (IL)-1alpha, IL-1beta, and tumor necrosis factor-alpha showed increased mRNA by 30 min after IT LPS instillation, but IL-6- and cytokine-induced neutrophil chemoattractant mRNAs were not substantially increased until 2 h after IT LPS instillation. Therefore, IT LPS causes differential NF-kappaB activation in air space cells and lung tissue, which likely determines production of key cytokines and directs the evolution of neutrophilic alveolitis.
Blackwell
T S
TS
Division of Allergy, Department of Medicine, Vanderbilt University School of Medicine, Nashville 37232-2650, USA.
Lancaster
L H
LH
Blackwell
T R
TR
Venkatakrishnan
A
A
Christman
J W
JW
D000818:Animals; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D006133:Growth Substances / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D007267:Injections; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea
D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D004731:Endotoxins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger