Expression of Toll-like receptor 4 is associated with enteroviral replication in human myocarditis
Abstract
Previous studies have demonstrated that inflammatory cytokine expression associated with enteroviral (EV) infection may play an important role in human myocarditis. However, the mechanism of the host immune response against viral pathogens has not been fully understood. The aim of the present study was to determine whether Toll-like receptor 4 (TLR4) and EV RNA are present in human myocarditis. Endomyocardial biopsy samples were obtained from 44 patients with myocarditis and five controls. Levels of plus- and minus-strand EV RNAs and TLR4 mRNA were measured by real-time reverse transcriptase–PCR. Immunohistochemical analysis was performed to identify the cellular source of TLR4 and the EV capsid protein VP1. EV RNA was present in 21 patients with myocarditis and these patients were defined as having either active viral replication (n=15) or latent viral persistence (n=6). Neither strand of EV RNA was detected in controls. TLR4 mRNA expression levels were higher in myocarditis patients than in controls (TLR4/glyceraldehyde-3-phosphate dehydrogenase ratio 1.48±0.17 compared with 0.08±0.06, P<0.001). A positive correlation was found between EV RNA and TLR4 levels (plus-strand vs TLR4: r=0.66, P<0.001; minus-strand vs TLR4: r=0.48, P<0.001). TLR4 immunostaining was observed in infiltrating cells and myocytes in patients with myocarditis. The EV capsid protein VP1 was also found in myocytes. The myocarditis group with EV replication and high levels of TLR4 showed significantly lower systolic function. The present study has shown that increased expression of TLR4 is associated with EV replication and that these RNA levels are related to cardiac dysfunction in human myocarditis.
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TLR4 is expressed in the heart of patients with myocarditis and DCM.
“TLR4 was also found to be expressed in the heart of patients with myocarditis and DCM. 166,167”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [166]
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- Authors
- SATOH, M., NAKAMURA, M., AKATSU, T., IWASAKA, J., SHIMODA, Y., SEGAWA, I., & HIRAMORI, K.
- Affiliations
- Iwate Medical University (JP)
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2003-06-01
- Volume
- 104
- Issue
- 6
- Pages
- 577-584
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W2001637648
- Cited by
- 63
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 7
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- TLR4, enterovirus replication, viral RNA, VP1 capsid protein, host immune response, myocarditis, systolic dysfunction, endomyocardial biopsy, viral persistence
- MeSH terms
- Adult, Enterovirus, Female, Humans, Immunohistochemistry, Male, Membrane Glycoproteins, Myocarditis, Myocardium, Receptors, Cell Surface, RNA, Messenger, RNA, Viral, Virus Replication, Gene Expression, Case-Control Studies, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Cardiac, Capsid Proteins, Toll-Like Receptors, Toll-Like Receptor 4
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