జర్నల్ ఆఫ్ అలెర్జీ & థెరపీ

నైరూప్య

Suppressive Activity of Histamine H1 Receptor Antagonists, Desloratadine and Levocetirizine, on the Production of Periostin from Nasal Epithelial Cells In vitro

Masayo Asano, Tomomi Mizuyoshi, Shintaro Ishikawa, Kazuhito Asano and Hitome Kobayashi

Background: Periostin, a 90-kDa endogenous extracellular matrix protein, is well known to be involved in the development and persistence of allergic rhinitis. Although histamine H1 receptor antagonists are recommended as first choice of agents in the treatment of allergic rhinitis, the influence of the agents on periostin production is not well understood. The present study was undertaken to examine the influence of histamine H1 receptor antagonists on periostin production from nasal epithelial cells after IL-4 stimulation in vitro.

Methods: Human nasal epithelial cells (HNEpC) at a concentration of 1 × 105 cells/ml were stimulated with 10.0 ng/ml IL-4 in combination with either desloratadine (DLT), loratadine (LT), levocetirizine (LCT) or cetirizine (CT). After 48 h, culture supernatants were collected and assayed for periostin levels by ELISA. The influence of LCT on transcription factor, STAT6, activation and periostin mRNA expression were also examined by ELISA and real-time RT-PCR, respectively.

Results: Treatment of cells with DLT, LT, LCT and CT suppressed the ability of HNEpC to produce periostin in response to IL-4 stimulation in dose-dependent manner. The minimum concentration that caused significant suppression is 0.01 mM for DLT, 0.05 mM for LT, 0.05 mM for LCT and 0.1 mM for CT. Treatment of HNEpC with LCT at more than 0.05 mM also suppressed STAT6 activation and periostin mRNA expression induced by IL-4 stimulation.

Conclusion: The present results strongly suggest that histamine H1 receptor antagonists favorably modify the clinical conditions of allergic rhinitis through the suppression of periostin production from nasal epithelial cells after IL-4 stimulation.