Cytomegalovirus induction of interleukin-6 in lung fibroblasts occurs independently of active infection and involves a G protein and the transcription factor, NF-kappaB.
Cytomegalovirus (CMV) infection induces the proinflammatory cytokine, interleukin (IL)-6, which may contribute to the pathology of the infection. In vitro CMV induction of IL-6 by human lung fibroblasts was studied. The quantity of cytokine in culture supernatants was maximal 20 h after infection and decreased thereafter. Transcription of the IL-6 gene and IL-6 protein expression were equally stimulated by infectious and UV-inactivated virus (CMV-UV). CMV-UV-stimulated IL-6 was inhibited by pyrrolidinedithiocarbamate (an inhibitor of the transcription factor, NF-kappaB) and by pertussis toxin (suggesting the involvement of a G protein) and occurred in the absence of CMV immediate-early antigen transcription. Neutralizing antibodies to IL-1beta or tumor necrosis factor-alpha did not affect CMV-UV-induced IL-6, but expression was inhibited by antibody to the CMV attachment glycoprotein. IL-6 production by fibroblasts occurs independently from productive infection but has characteristics that suggest a ligand receptor-mediated pathway. This function may be important in pathology or disease resolution.
Carlquist
J F
JF
Molecular Pathology, LDS Hospital, Salt Lake City, UT 84143, USA. LDJCARLQ@IHC.COM.
Edelman
L
L
Bennion
D W
DW
Anderson
J L
JL
D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology* / Q000528:radiation effects; D005347:Fibroblasts; D019204:GTP-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008168:Lung / Q000166:cytology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays; D014759:Viral Envelope Proteins / Q000276:immunology / Q000502:physiology
D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; D019204:GTP-Binding Proteins