Procaterol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells |
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Authors: | Yamaya Mutsuo Nishimura Hidekazu Hatachi Yukimasa Yoshida Motoki Fujiwara Hidenori Asada Masanori Nakayama Katsutoshi Yasuda Hiroyasu Deng Xue Sasaki Takahiko Kubo Hiroshi Nagatomi Ryoichi |
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Affiliation: | aDepartment of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Japan;bVirus Research Center, Clinical Research Division, Sendai National Hospital, Sendai 983-8520, Japan;cDepartment of Respiratory Medicine, Graduate School of Medicine Kyoto University, Kyoto 606-8507, Japan;dDepartment of Geriatrics and Gerontology, Institute of Ageing and Cancer, Tohoku University, Sendai 980-8574, Japan;eCenter for Asian Traditional Medicine, Tohoku University Graduate School of Medicine, Japan;fDivision of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan;gDepartment of Innovation of New Biomedical Engineering Center, Tohoku University, 980-8574, Japan;hDepartment of Respiratory Medicine, Tohoku University School of Medicine, 980-8574, Japan;iMedicine and Science in Sports and Exercise, Tohoku University School of Medicine, Sendai 980-8575, Japan |
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Abstract: | β2 agonists reduce the frequency of exacerbations in patients with bronchial asthma and chronic obstructive pulmonary disease caused by respiratory virus infection. β2 agonists reduce the production of pro-inflammatory cytokines. However, the inhibitory effects of β2 agonists on the infection of rhinovirus, the major cause of exacerbations, have not been well studied. To examine the effects of a β2 agonist, procaterol, on rhinovirus infection and rhinovirus infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group rhinovirus, type 14 rhinovirus. Rhinovirus infection increased viral titers and the content of pro-inflammatory cytokines, including interleukin-1β and interlukin-6, in supernatant fluids and rhinovirus RNA in the cells. Procaterol reduced rhinovirus titers and RNA, cytokine concentrations, and susceptibility to rhinovirus infection. Procaterol reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for type 14 rhinovirus, and the number of acidic endosomes in the cells from which rhinovirus RNA enters into the cytoplasm. Procaterol inhibited the activation of nuclear factor kappa-B (NF-κB) proteins including p50 and p65 in the nuclear extracts, while it increased the cytosolic amount of the inhibitory kappa B-α and intracellular cyclic AMP (cAMP) levels. A selective β2-adrenergic receptor antagonist ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol] reversed the inhibitory effects of procaterol on rhinovirus titers and RNA, susceptibility to rhinovirus infection, pro-inflammatory cytokines production, ICAM-1 expression, acidic endosomes, and NF-κB. ICI 118551 also reversed the effects of procaterol on cAMP levels. Procaterol may inhibit rhinovirus infection by reducing ICAM-1 and acidic endosomes as well as modulate airway inflammation in rhinovirus infection. |
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Keywords: | Procaterol Human tracheal epithelial cell Rhinovirus Intercellular adhesion molecule Acidic endosome Pro-inflammatory cytokine |
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