The proton pump inhibitor lansoprazole inhibits rhinovirus infection in cultured human tracheal epithelial cells.
To examine the effects of lansoprazole, a proton pump inhibitor, on rhinovirus infection in airways, human tracheal epithelial cells were infected with a major subgroup of rhinoviruses, type 14 rhinovirus. Rhinovirus increased the mRNA expression of intercellular adhesion molecule-1 (ICAM-1) in the cells, the major rhinovirus receptor, and the content of the soluble form of ICAM-1 (sICAM-1) and cytokines in supernatants. Lansoprazole reduced supernatant titers and RNA of rhinovirus, the susceptibility to rhinovirus infection, the ICAM-1 mRNA production, the number and fluorescence intensity of acidic endosomes in the cells, and supernatants sICAM-1 and cytokine concentrations including interleukin-1beta. Antibody to interleukin-1beta reduced baseline and rhinovirus-induced ICAM-1 production. These results suggest that lansoprazole inhibits rhinovirus infection by reducing ICAM-1 via partly endogenous production of interleukin-1beta, and by blocking the rhinovirus RNA entry into the endosomes. Lansoprazole may modulate airway inflammation by reducing the production of cytokines and ICAM-1 in rhinovirus infection.
Sasaki
Takahiko
T
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yamaya
Mutsuo
M
Yasuda
Hiroyasu
H
Inoue
Daisuke
D
Yamada
Mitsuhiro
M
Kubo
Hiroshi
H
Nishimura
Hidekazu
H
Sasaki
Hidetada
H
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000368:Aged; D000890:Anti-Infective Agents / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D064747:Lansoprazole; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D014132:Trachea / Q000166:cytology
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000890:Anti-Infective Agents; D016207:Cytokines; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D064747:Lansoprazole; D018799:Intercellular Adhesion Molecule-1; D009853:Omeprazole