title: Magnitude of influenza virus replication and cell damage is associated with interleukin-6 production in primary cultures of human tracheal epithelium.
abstract: Primary cultures of human tracheal epithelium were infected with influenza viruses to examine the relationships between the magnitude of viral replication and infection-induced cell damage and cytokine production in airway epithelial cells. Infection with four strains of the type A influenza virus increased the detached cell number and lactate dehydrogenase (LDH) levels in the supernatants. The detached cell number and LDH levels were related to the viral titers and interleukin (IL)-6 levels and the nuclear factor kappa B (NF-κB) p65 activation. Treatment of the cells with an anti-IL-6 receptor antibody and an NF-κB inhibitor, caffeic acid phenethyl ester, reduced the detached cell number, viral titers and the LDH levels and improved cell viability after infection with the pandemic influenza virus [A/Sendai-H/N0633/2009 (H1N1) pdm09]. A caspase-3 inhibitor, benzyloxycarbonyl-DEVD-fluoromethyl ketone, reduced the detached cell number and viral titers. Influenza viral infection-induced cell damage may be partly related to the magnitude of viral replication, NF-κB-p65-mediated IL-6 production and caspase-3 activation.
authors: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: myamaya@med.tohoku.ac.jp.
authors: Mutsuo
authors: M
authors: Yamaya
authors: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Lusamba K
authors: LK
authors: Nadine
authors: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Chiharu
authors: C
authors: Ota
authors: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Hiroshi
authors: H
authors: Kubo
authors: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Tomonori
authors: T
authors: Makiguchi
authors: Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Ryoichi
authors: R
authors: Nagatomi
authors: Virus Research Center, Clinical Research Division, Sendai National Hospital, Sendai 983-8520, Japan.
authors: Hidekazu
authors: H
authors: Nishimura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000403:Airway Resistance; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002415:Cats; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014132:Trachea / Q000473:pathology*; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D000906:Antibodies; D003374:Coumarins; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009842:Oligopeptides; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014764:Viral Proteins; C106566:benzyloxycarbonyl-aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin; D007770:L-Lactate Dehydrogenase
keywords: Airway epithelial cells; Cell damage; Influenza virus; Interleukin-6; Pathogenicity