TY - JOUR
T1 - Ambroxol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells
AU - Yamaya, Mutsuo
AU - Nishimura, Hidekazu
AU - Nadine, Lusamba Kalonji
AU - Ota, Chiharu
AU - Kubo, Hiroshi
AU - Nagatomi, Ryoichi
N1 - Funding Information:
Conflict of interest All authors have no conflict of interest. Mutsuo Yamaya is a professor and Hiroshi Kubo is an associate professor in the Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine. This department is funded by eleven pharmaceutical companies: Teijin Pharma Co., Ltd., Kyorin Pharmaceutical Co. Ltd., Abbott Japan, Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., AstraZeneca K.K., Daiichi Sankyo Co. Ltd., Otsuka Pharmaceutical Co. Ltd., GlaxoSmithKline K.K. Co., Ltd., Tanabe Mitsubishi Pharmaceutical Co., Ltd., Ono Yakuhin Co. Ltd., and Nippon Boehringer-Ingelheim Co., Ltd.
Funding Information:
Acknowledgments This study was supported by Health, Labour and Welfare Sciences Research Grants for Research on Measures for Intractable Diseases from the Japanese Government, and Teijin Pharma Co. Ltd.
PY - 2014/4
Y1 - 2014/4
N2 - The mucolytic drug ambroxol hydrochloride reduces the production of pro-inflammatory cytokines and the frequency of exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, the inhibitory effects of ambroxol on rhinovirus infection, the major cause of COPD exacerbations, have not been studied. We examined the effects of ambroxol on type 14 rhinovirus (RV14) infection, a major RV group, in primary cultures of human tracheal epithelial cells. RV14 infection increased virus titers and cytokine content in the supernatants and RV14 RNA in the cells. Ambroxol (100 nM) reduced RV14 titers and cytokine concentrations of interleukin (IL)-1β, IL-6 and IL-8 in the supernatants and RV14 RNA in the cells after RV14 infection, in addition to reducing susceptibility to RV14 infection. Ambroxol also reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14, and the number of acidic endosomes from which RV14 RNA enters the cytoplasm. In addition, ambroxol reduced the activation of the transcription factor nuclear factor kappa B (NF-κB) in the nucleus. These results suggest that ambroxol inhibits RV14 infection partly by reducing ICAM-1 and acidic endosomes via the inhibition of NF-κB activation. Ambroxol may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.
AB - The mucolytic drug ambroxol hydrochloride reduces the production of pro-inflammatory cytokines and the frequency of exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, the inhibitory effects of ambroxol on rhinovirus infection, the major cause of COPD exacerbations, have not been studied. We examined the effects of ambroxol on type 14 rhinovirus (RV14) infection, a major RV group, in primary cultures of human tracheal epithelial cells. RV14 infection increased virus titers and cytokine content in the supernatants and RV14 RNA in the cells. Ambroxol (100 nM) reduced RV14 titers and cytokine concentrations of interleukin (IL)-1β, IL-6 and IL-8 in the supernatants and RV14 RNA in the cells after RV14 infection, in addition to reducing susceptibility to RV14 infection. Ambroxol also reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14, and the number of acidic endosomes from which RV14 RNA enters the cytoplasm. In addition, ambroxol reduced the activation of the transcription factor nuclear factor kappa B (NF-κB) in the nucleus. These results suggest that ambroxol inhibits RV14 infection partly by reducing ICAM-1 and acidic endosomes via the inhibition of NF-κB activation. Ambroxol may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.
KW - Airway epithelium
KW - Ambroxol
KW - Infection control
KW - Inflammation
KW - Intercellular adhesion molecule-1 (ICAM-1)
KW - Rhinovirus
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U2 - 10.1007/s12272-013-0210-7
DO - 10.1007/s12272-013-0210-7
M3 - Article
C2 - 23856970
AN - SCOPUS:84897546091
VL - 37
SP - 520
EP - 529
JO - Archives of Pharmacal Research
JF - Archives of Pharmacal Research
SN - 0253-6269
IS - 4
ER -