Effect of budesonide and azelastine on histamine signaling regulation in human nasal epithelial cells.
Both glucocorticoids and H1-antihistamines are widely used on patients with airway diseases. However, their direct effects on airway epithelial cells are not fully explored. Therefore, we use the primary culture of human nasal epithelial cells (HNEpC) to delineate in vitro mucosal responses to above two drugs. HNEpC cells were cultured with/without budesonide and azelastine. The growth rate at each group was recorded and measured as population double time (PDT). The histamine1-receptor (H1R), muscarinic1-receptor (M1R) and M3R were measured using immunocytochemistry and western blotting after 7-days treatment. Then, we used histamine and methacholine to stimulate the mucus secretion from HNEpC and observed the MUC5AC expression in culture supernatants. Concentration-dependent treatment-induced inhibition of HNEpC growth rate was observed. Cells incubated with azelastine proliferated significantly slower than that with budesonide and the combined use of those drugs led to significant PDT prolong. The immunocytochemistry showed the H1R, M1R and M3R were obviously located in the cell membrane without apparent difference after treatment. However, western blotting showed that budesonide can significantly up-regulate the H1R, M1R and M3R level while azelastine had opposite effects. Histamine and methacholine stimulated MUC5AC secretion was greater in cells treated with budesonide but was lesser in those treated with azelastine, as compared to controls. Our data suggest that both budesonide and azelastine can significantly inhibit HNEpC proliferation, and therefore, be helpful in against airway remodeling. Long-term use of budesonide might amplify histamine signaling and result in airway hyperreactivity to stimulants by enhancing H1R, M1R and M3R expression while azelastine can oppose this effect. Therefore, combined use of those two drugs in patients with chronic inflammatory airway diseases may be an ideal option.
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.|Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Shao-Cheng
SC
Liu
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.|Department of Radiation Oncology, Taipei Medical University, Taipei, Taiwan, ROC.
Chun-Shu
CS
Lin
Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Shyi-Gen
SG
Chen
Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Yueng-Hsiang
YH
Chu
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Fei-Peng
FP
Lee
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.|Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Hsuan-Hsuan
HH
Lu
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC. w0512n@ms15.hinet.net.|Department of Otolaryngology-Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC. w0512n@ms15.hinet.net.|Department of Otolaryngology-Head and Neck Surgery, Shuang Ho Hospital, No. 291, Zhongzheng Rd., Zhonghe District, New Taipei City, 23561, Taiwan, ROC. w0512n@ms15.hinet.net.
Hsing-Won
HW
Wang
D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D015415:Biomarkers; D005938:Glucocorticoids; D039563:Histamine H1 Antagonists, Non-Sedating; D010793:Phthalazines; D019819:Budesonide; D006632:Histamine; C020976:azelastine
Airway remodeling; Antihistamine; Glucocorticoid; Histamine receptor; Muscarinic receptor