Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation.
To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF-kappa B site in this promoter. An NF-kappa B-DNA binding activity, mediated by p65, p50, and p52 NF-kappa B moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation IL-6 production is mediated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-kappa B activation is likely to be an important event in RV-induced pathologies.
Zhu
Z
Z
Yale University School of Medicine, Department of Internal Medicine, New Haven, Connecticut 06520-8057, USA.
Tang
W
W
Ray
A
A
Wu
Y
Y
Einarsson
O
O
Landry
M L
ML
Gwaltney
J
J
Elias
J A
JA
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D003139:Common Cold / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology; D009297:Nasal Mucosa / Q000276:immunology; D015345:Oligonucleotide Probes / Q000737:chemistry; D010850:Picornaviridae Infections / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012229:Rhinovirus / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D012333:RNA, Messenger