Transient Induction of Cytokine Production in Human Myocardial Fibroblasts by Coxsackievirus B3

Abstract

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-␤ 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-␤ was suppressed by CVB3. (Circ Res. 2000;86:753-759.)

Coxsackievirus Group B Type 3 Infection Upregulates Expression of Monocyte Chemoattractant Protein 1 in Cardiac Myocytes, Which Leads to Enhanced Migration of Mononuclear Cells in Viral Myocarditis

“…Numerous previous studies have suggested that virus replication is required for the induction and upregulation of chemokines by virus infection (3,9,20). To test whether CVB3 replication is required for MCP-1 upregulation, CVB3 was exposed to UV irradiation for 1.5 h, and the replication ability of CVB3 was completely abolished (data not shown).…”

“…Viruses are known to be potent stimulators of chemokine expression in vitro and in vivo (3,20). It is believed that virus replication is required for virus-induced expression of chemokines (9).…”

Cross-Reactivity of Anti-CagA Antibodies With Vascular Wall Antigens

“…AntiCagA antibodies could then bind the exposed vascular antigens and further contribute to the activation of inflammatory cells within lesions. Production of cytokines and other inflammatory mediators by activated macrophages and fibroblasts [31][32][33] could then lead to the destabilization of atherosclerotic plaques, possibly triggering ischemic events.…”

The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism

“…On the other hand, the role of NCNI cells in EAM has not yet been fully examined. Myocardial fibroblasts in coxsackievirus B3 myocarditis produce pro-inflammatory cytokines [30]. In rheuma- toid arthritis, fibroblasts were thought to play an important role in cartilage damage [31].…”