title: NF-kappa B is activated during acute inflammation in vivo in association with elevated endothelial cell adhesion molecule gene expression and leukocyte recruitment.
abstract: Leukocytes accumulate at sites of inflammation in response to the induced expression of endothelial cell adhesion molecules. The nuclear transcription factor kappa B (NF-kappa B) plays a critical role in the cytokine-induced expression of these genes in cultured endothelium. We examined the relationship between NF-kappa B activation and endothelial cell adhesion molecule gene expression in vivo during the initiation of acute inflammation. Nuclear NF-kappa B DNA-binding activity was rapidly increased within lung and heart tissues of rats administered endotoxin, consistent with the translocation of NF-kappa B complexes from the cytoplasm to the nucleus. This NF-kappa B was composed of p50 and p65 subunits, and could bind NF-kappa B elements in the E-selectin promoter. NF-kappa B activation was maximal within 30 min and persisted for at least 3 hr after endotoxin treatment. NF-kappa B activation preceded the transcriptional activation of the P-selectin, E-selectin, VCAM-1, and ICAM-1 genes. In the lung, increased expression of P-selectin and ICAM-1 protein was detected immunohistochemically. These molecular events were temporally associated with the sequestration of leukocytes and the development of pulmonary inflammation. NF-kappa B activation is therefore an early event in the initiation of acute inflammation in vivo. This molecular pathway may be of consequence in the pathogenesis of acute inflammatory disease.
authors.affiliation: Cell Biology and Inflammation Research, Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan 49001, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Manning
authors.forename: F P
authors.initials: FP
authors.lastname: Bell
authors.forename: C L
authors.initials: CL
authors.lastname: Rosenbloom
authors.forename: J G
authors.initials: JG
authors.lastname: Chosay
authors.forename: C A
authors.initials: CA
authors.lastname: Simmons
authors.forename: J L
authors.initials: JL
authors.lastname: Northrup
authors.forename: R J
authors.initials: RJ
authors.lastname: Shebuski
authors.forename: C J
authors.initials: CJ
authors.lastname: Dunn
authors.forename: D C
authors.initials: DC
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D004731:Endotoxins / Q000494:pharmacology; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology; D007150:Immunohistochemistry; D007962:Leukocytes / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015815:Cell Adhesion Molecules; D004731:Endotoxins; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D019007:P-Selectin; D009195:Peroxidase