Suppression of osteopontin functions by levocetirizine, a histamine H1 receptor antagonist, in vitro.
OBJECTIVE
Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro.


METHODS
Human nasal epithelial cells (5 × 10(5) cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively.


RESULTS
The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF- κ B and AP-1, activation, which were increased by the stimulation of cells with OPN.


CONCLUSIONS
The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases.
Department of Otorhinolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Toshimitsu
T
Komatsuzaki
Department of Otorhinolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Isao
I
Suzaki
Department of Otorhinolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Kojiro
K
Hirano
Department of Otorhinolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Ken-Ichi
K
Kanai
Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama 226-8555, Japan.
Kazuhito
K
Asano
Department of Otorhinolaryngology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Harumi
H
Suzaki
D017332:Cetirizine / Q000008:administration & dosage*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism
D006634:Histamine H1 Antagonists; D012333:RNA, Messenger; D053495:Osteopontin; C472067:levocetirizine; D017332:Cetirizine