Toluene diisocyanate (TDI) induces production of inflammatory cytokines and chemokines by bronchial epithelial cells via the epidermal growth factor receptor and p38 mitogen-activated protein kinase pathways.
Toluene diisocyanate (TDI) is known as one of causes of occupational asthma and hypersensitivity pneumonitis. To investigate the stimulatory effect on bronchial epithelial cells in response to TDI, the authors examined production of cytokines by the bronchial epithelial cell line BEAS-2B and intercellular signal transduction stimulated by TDI-human serum albumin (HSA) conjugate. The production of interleukin (IL)-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and regulated on activation normal T cell expressed and secreted (RANTES) from the bronchial epithelial cells were augmented by the TDI-HSA conjugate. Extracellular signal-regulated kinase (Erk) 1/2 and p38 mitogen-activated protein kinase (MAPK) were phosphorylated by the TDI-HSA conjugate. AG1478, SB203580, and dexamethasone prevented augmentation of these cytokine production. TDI-HSA conjugate did not augment release of epidermal growth factor (EGF) ligands from BEAS-2B. These results suggest that TDI directly induces production of proinflammatory cytokines and chemokines through p38 MAPK and EGF receptor (EGFR)-Erk pathway without an autocrine mechanism. Thus, TDI was shown to have a stimulatory effect on bronchial epithelial cells, suggesting the potent role of bronchial epithelial cells in TDI-induced asthma.
Ogawa
Hirohisa
H
Department of Clinical Investigation, National Hospital Organization National Kochi Hospital, Kochi City, Japan. ogawah@clin.med.tokushima-u.ac.jp
Inoue
Shizuka
S
Ogushi
Fumitaka
F
Ogura
Hideo
H
Nakamura
Yoichi
Y
D000485:Allergens / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D011799:Quinazolines; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D012709:Serum Albumin / Q000276:immunology / Q000633:toxicity; D015398:Signal Transduction; D014051:Toluene 2,4-Diisocyanate / Q000276:immunology / Q000633:toxicity*; D020032:Tyrphostins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000485:Allergens; D018925:Chemokines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D011799:Quinazolines; D012709:Serum Albumin; D020032:Tyrphostins; C101044:RTKI cpd; D014051:Toluene 2,4-Diisocyanate; D003907:Dexamethasone; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580