Logo image
Transient induction of cytokine production in human myocardial fibroblasts by coxsackievirus B3
Journal article   Open access   Peer reviewed

Transient induction of cytokine production in human myocardial fibroblasts by coxsackievirus B3

A Heim, S Zeuke, S Weiss, W Ruschewski and I M Grumbach
Circulation research, Vol.86(7), pp.753-759
04/14/2000
DOI: 10.1161/01.RES.86.7.753
PMID: 10764408
url
https://doi.org/10.1161/01.RES.86.7.753View
Published (Version of record) Open Access

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-1alpha transcription of myocardial fibroblasts was not significantly increased, IL-1alpha was released from cells to culture supernatants 5 days after infection. Furthermore, a suppression of interferon-beta 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-beta was suppressed by CVB3.
Transfection Interleukin-1 - genetics Interleukin-8 - genetics Myocardium - immunology Interleukin-6 - genetics Fibroblasts - physiology Gene Expression Regulation - immunology Interleukin-8 - biosynthesis Humans Cells, Cultured Interferon-beta - biosynthesis Interleukin-1 - biosynthesis Myocardium - cytology Reverse Transcriptase Polymerase Chain Reaction - methods Enterovirus B, Human - immunology Interferon-beta - genetics Interleukin-6 - biosynthesis Enterovirus B, Human - genetics Fibroblasts - cytology Cytokines - genetics

Details

Metrics

Logo image