title: Activator protein-1 activation in acute lung injury.
abstract: The role of activator protein-1 (AP-1) in inflammation is primarily unknown. AP-1 was evaluated in nuclear extracts from alveolar macrophages and whole lung nuclear extracts during acute lung injury after deposition of IgG immune complexes. AP-1 activation occurred in macrophages and in whole lung extracts, but with distinctly different time courses. Low levels of constitutive AP-1 were observed in normal rat lung as determined by the electrophoretic mobility shift assay. Increased AP-1 was detected 2 hours after initiation of the inflammatory response in lung with a further increase by 4 hours, while AP-1 activation was found in alveolar macrophages 0.5 hour after onset of the inflammatory response. mRNAs and proteins for c-fos, c-jun, jun-B, and jun-D were all up-regulated in whole lung tissues and in alveolar macrophages during acute lung injury induced by IgG immune complex deposition. Depletion of lung macrophages sharply reduced AP-1 activation, as did anti-tumor necrosis factor-alpha, whereas complement depletion showed no effect on lung AP-1 activation. The data suggest that activation of AP-1 occurs in both alveolar macrophages and in the lung, and this activation process is macrophage- and tumor necrosis factor-alpha-dependent.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.
authors.forename: Ren-Feng
authors.initials: RF
authors.lastname: Guo
authors.forename: Alex B
authors.initials: AB
authors.lastname: Lentsch
authors.forename: J Vidya
authors.initials: JV
authors.lastname: Sarma
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Niels C
authors.initials: NC
authors.lastname: Riedemann
authors.forename: Shannon D
authors.initials: SD
authors.lastname: McClintock
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: McGuire
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D000208:Acute Disease; D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D003165:Complement System Proteins