Title | The proton ATPase inhibitor bafilomycin A1 reduces the release of rhinovirus C and cytokines from primary cultures of human nasal epithelial cells. | ||
Author | Yamaya, Mutsuo; Deng, Xue; Kikuchi, Akiko; Sugawara, Mitsuru; Saito, Natsumi; Kubo, Toru; Momma, Haruki; Kawase, Tetsuaki; Nakagome, Kazuyuki; Shimotai, Yoshitaka; Nishimura, Hidekazu | ||
Journal | Virus Res | Publication Year/Month | 2021-Oct |
PMID | 34425162 | PMCID | -N/A- |
Affiliation + expend | 1.Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Virus Research Center, Clinical Research Division, Sendai Medical Center, Sendai 983-8520, Japan. Electronic address: myamaya@med.tohoku.ac.jp. |
Rhinovirus species C (RV-C) causes more severe asthma attacks than other rhinovirus species. However, the modulation of RV-C replication by drugs has not been well studied. Primary human nasal epithelial (HNE) cells cultured on filter membranes with air-liquid interface methods were infected with RV-C03, and the levels of RV-C03 RNA collected from the airway surface liquid (ASL) of HNE cells were measured with a SYBR Green assay. Pretreatment of HNE cells with the specific vacuolar H(+)-ATPase inhibitor bafilomycin A1 reduced the RV-C03 RNA levels in the ASL; inflammatory cytokines, including interleukin (IL)-1beta, IL-6 and IL-8, in the supernatant; the mRNA expression of the RV-C receptor cadherin-related family member 3 (CDHR3) in the cells; and the number of acidic endosomes where RV-B RNA enters the cytoplasm. The levels of RV-C03 RNA in the ASL obtained from HNE cells with the CDHR3 rs6967,330 G/A genotype tended to be higher than those obtained from HNE cells with the G/G genotype. Pretreatment with the Na(+)/H(+) exchanger inhibitor ethyl-isopropyl amiloride or either of the macrolides clarithromycin or EM900 also reduced RV-C03 RNA levels in the ASL and the number of acidic endosomes in HNE cells. In addition, significant levels of RV-A16, RV-B14 and RV-C25 RNA were detected in the ASL, and bafilomycin A1 also decreased the RV-C25 RNA levels. These findings suggest that bafilomycin A1 may reduce the release of RV-Cs and inflammatory cytokines from human airway epithelial cells. RV-Cs may be sensitive to drugs, including bafilomycin A1, that increase endosomal pH, and CDHR3 may mediate virus entry through receptor-mediated endocytosis in human airway epithelial cells.