Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells.
The human nasal epithelium is the first line of defense during respiratory virus infection. Respiratory syncytial virus (RSV) is the major cause of bronchitis, asthma and severe lower respiratory tract disease in infants and young children. We previously reported in human nasal epithelial cells (HNECs), the replication and budding of RSV and the epithelial responses, including release of proinflammatory cytokines and enhancement of the tight junctions, are in part regulated via an NF-κB pathway. In this study, we investigated the effects of the NF-κB in HNECs infected with RSV. Curcumin prevented the replication and budding of RSV and the epithelial responses to it without cytotoxicity. Furthermore, the upregulation of the epithelial barrier function caused by infection with RSV was enhanced by curcumin. Curcumin also has wide pharmacokinetic effects as an inhibitor of NF-κB, eIF-2α dephosphorylation, proteasome and COX2. RSV-infected HNECs were treated with the eIF-2α dephosphorylation blocker salubrinal and the proteasome inhibitor MG132, and inhibitors of COX1 and COX2. Treatment with salubrinal, MG132 and COX2 inhibitor, like curcumin, prevented the replication of RSV and the epithelial responses, and treatment with salubrinal and MG132 enhanced the upregulation of tight junction molecules induced by infection with RSV. These results suggest that curcumin can prevent the replication of RSV and the epithelial responses to it without cytotoxicity and may act as therapy for severe lower respiratory tract disease in infants and young children caused by RSV infection.
Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, Japan ; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Kazufumi
K
Obata
Takashi
T
Kojima
Tomoyuki
T
Masaki
Tamaki
T
Okabayashi
Shinichi
S
Yokota
Satoshi
S
Hirakawa
Kazuaki
K
Nomura
Akira
A
Takasawa
Masaki
M
Murata
Satoshi
S
Tanaka
Jun
J
Fuchimoto
Nobuhiro
N
Fujii
Hiroyuki
H
Tsutsumi
Tetsuo
T
Himi
Norimasa
N
Sawada
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002675:Child, Preschool; D002934:Cinnamates / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D015852:Eukaryotic Initiation Factor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002934:Cinnamates; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D007976:Leupeptins; D016328:NF-kappa B; C496827:salubrinal; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D046988:Proteasome Endopeptidase Complex; D013890:Thiourea; D003474:Curcumin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde