Activator protein-1 activation in acute lung injury.
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.
Guo
Ren-Feng
RF
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0602, USA.
Lentsch
Alex B
AB
Sarma
J Vidya
JV
Sun
Lei
L
Riedemann
Niels C
NC
McClintock
Shannon D
SD
McGuire
Stephanie R
SR
Van Rooijen
Nico
N
Ward
Peter A
PA
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
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