© 2000 American Heart Association, Inc.
Cellular Biology |
Transient Induction of Cytokine Production in Human Myocardial Fibroblasts by Coxsackievirus B3
From the Institut für Virologie und Seuchenhygiene (A.H., S.Z., S.W.), Medizinsche Hochschule, Hannover, Germany; Abteilung für Thorax-, Herz-, und Gefässchirurgie (W.R.), Georg-August-Universität Göttingen, Germany; and Department of Medicine (I.M.G.), Section of Hematology/Oncology, University of Illinois at Chicago, Ill.
Correspondence to Dr Albert Heim, Institut für Virologie und Seuchenhygiene, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, FRG. E-mail ahei{at}virologie.mh-hannover.de
Abstract—Cytokine
expression in enterovirus infections of the heart may trigger
inflammation and have detrimental effects on myocytes. However, the
induction of cytokines in human myocardial cells by
cardiotropic enteroviruses, for example, Coxsackievirus B3 (CVB3), was
not yet demonstrated. Fibroblasts are the predominant cell type of the
myocardial interstitium before inflammatory infiltration develops.
Hence, we investigated, by enzyme immunoassays, reverse
transcription–quantitative polymerase chain reaction (RT-qPCR), and
nucleic acid sequence–based amplification (NASBA), whether CVB3
induces cytokine expression in cultured human myocardial
fibroblasts. As early as 3 hours after infection, RT-qPCR demonstrated
a 2-fold increase of interleukin (IL)–6 and IL-8 mRNA compared with
basal transcription, resulting in a significant increase of IL-6 and
IL-8 to a median level of 1500 pg/mL (range, 1246 to 1858) and 529
pg/mL (range, 428 to 601) in culture supernatants, respectively. IL-6
and IL-8 expression returned to basal levels within 3 and 5 days,
respectively, despite a persistent (carrier-state) CVB3 infection. For
comparison, IL-6 and IL-8 were induced in dermal fibroblasts later than
3 days after CVB3 infection. Although the low-level IL-1
transcription of myocardial fibroblasts was not significantly
increased, IL-1 was released from cells to culture supernatants 5
days after infection. Furthermore, a suppression of interferon-ß
transcription was demonstrated up to 24 hours after CVB3 infection of
myocardial fibroblasts by highly sensitive NASBA. In conclusion, our
results demonstrate a heart-specific pattern of a rapid and transient
induction of proinflammatory cytokines after CVB3 infection,
whereas the expression of protective interferon-ß was suppressed
by CVB3.
Key Words: fibroblasts • interferon • interleukin • myocarditis • gene expression
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