Increased expression of p38 MAPK in human bronchial epithelium after lipopolysaccharide exposure.
Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to LPS has been shown to induce neutrophilic airway inflammation in humans. The aim of this investigation was to study the early inflammatory responses to LPS exposure in human airway mucosa in vivo. In total, 15 healthy nonsmoking volunteers participated. Bronchoscopy was performed on two separate occasions, 3 h after saline inhalation and after inhalation of 50 mug LPS in saline. Endobronchial mucosal biopsy specimens were taken and stained immunohistochemically using a panel of monoclonal antibodies directed against mitogen-activated protein kinases (MAPKs), transcription factors, cytokines, adhesion molecules and inflammatory cells. Expression of p38 MAPK increased as a consequence of LPS exposure, as determined by both total epithelial staining and nuclear location. These two responses were strongly associated. Epithelial expression of interleukin-8 showed a tendency towards a significant increase after LPS compared to saline. Epithelial mast cell numbers were increased after LPS, whereas neutrophil numbers were unchanged. Inhalation of lipopolysaccharide induced activation of the bronchial epithelium, as demonstrated 3 h after exposure by increased expression of p38 mitogen-activated protein kinase and interleukin-8, and may represent early regulatory steps in the subsequent development of a neutrophilic bronchial inflammation.
Roos-Engstrand
E
E
Dept of Respiratory Medicine and Allergy, University Hospital, SE-901 85 Umeå, Sweden.
Wallin
A
A
Bucht
A
A
Pourazar
J
J
Sandström
T
T
Blomberg
A
A
D000328:Adult; D001991:Bronchitis / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D020545:Respiratory Mucosa / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016207:Cytokines; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases