Proinflammatory cytokine-induced and chemical mediator-induced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase-dependent pathway.
The p38 mitogen-activated protein (MAP) kinase is activated in various cells by proinflammatory cytokines and environmental stresses. However, little is known about the role of p38 MAP kinase in proinflammatory cytokine- and chemical mediator-induced cytokine expression in human bronchial epithelial cells (BECs). In this study we examined the role of p38 MAP kinase in IL-8 expression in BECs to clarify the signal transduction pathway regulating IL-8 expression in BECs stimulated with tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and platelet-activating factor (PAF). We used TNF-alpha, IL-1alpha, and PAF as inducers for the analysis of the signal transduction pathway and determined IL-8 expression in BECs because TNF-alpha, IL-1alpha, and PAF are known to induce cytokine expression in BECs, and these proinflammatory cytokines and PAF are described to have a role in the production of allergic inflammation. The results showed that TNF-alpha, IL-1alpha, and PAF induced tyrosine phosphorylation of p38 MAP kinase in a dose- and time-dependent manner. The specific p38 MAP kinase inhibitor, SB 203580, completely inhibited TNF-alpha-, IL-1alpha-, or PAF-induced IL-8 protein and mRNA expression in BECs. These results indicated that p38 MAP kinase plays an important role in TNF-alpha-, IL-1alpha-, or PAF-activated signaling pathway, which regulates IL-8 expression in BECs. In addition, these results provide new evidence on a strategy for treatment of airway inflammation with the specific p38 MAP kinase inhibitor.
Matsumoto
K
K
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Hashimoto
S
S
Gon
Y
Y
Nakayama
T
T
Horie
T
T
D001980:Bronchi / Q000276:immunology* / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases; D010972:Platelet Activating Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D007375:Interleukin-1; D016209:Interleukin-8; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases