Induction of a broad spectrum of inflammation-related genes by Coxsackievirus B3 requires Interleukin-1 signaling
| Autor: | Barbara Ritter, Semra Kati, Albert Heim, Andreas Henke, Fabienne Rehren, Elena Lam, Michael Kracht, Oliver Dittrich-Breiholz |
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| Rok vydání: | 2011 |
| Předmět: |
Microbiology (medical)
Immunology Inflammation Enzyme-Linked Immunosorbent Assay Biology CCL2 Real-Time Polymerase Chain Reaction Proinflammatory cytokine Cell Line Paracrine signalling medicine Immunology and Allergy Humans Autocrine signalling Gene knockdown Gene Expression Profiling HEK 293 cells Interleukin General Medicine Fibroblasts Microarray Analysis Enterovirus B Human Cancer research medicine.symptom Interleukin-1 Signal Transduction |
| Zdroj: | Medical microbiology and immunology. 202(1) |
| ISSN: | 1432-1831 |
| Popis: | Coxsackievirus B3 (CVB3) is a major cause of acute and chronic forms of myocarditis. Previously, direct viral injury and post-infectious autoimmune response were suspected as main pathogenetic mechanisms. However, induction of pro-inflammatory cytokines may be crucial for pathogenesis in spite of host protein shut off caused by CVB3 replication. We investigated the global expression profile of pro-inflammatory genes induced by acute and persistent (carrier state) CVB3 infection in human fibroblast cell cultures with DNA microarrays, quantitative RT-PCR and ELISA. Rapid induction of a typical spectrum of about 30 inflammation-related genes (e.g., PTGS2, CCL2, IL-1β, IL-6, IL-8, CSF2, MMP-1, MMP-3, and MMP-15) suggested an essential, autocrine role of IL-1. This hypothesis was confirmed by over-expression of IL-1RI, which resulted in a cytokine response upon CVB3 infection in HEK 293 cells otherwise refractory to CVB3-caused gene expression. Blocking IL-1 receptor type I (IL-1RI)-signaling during CVB3 infection with an IL-1 receptor antagonist (IL-1ra) as well as knockdown of IL-1RI using siRNA abrogated cytokine response in human fibroblasts. Both IL-1α and IL-1β are relevant for the induction of inflammation-related genes during CVB3 infection as shown by neutralization experiments. Paracrine effects of IL-1 on the subset of non-infected cells in carrier state infected fibroblast cultures enhanced induction of inflammation-related genes. Conclusions: A broad spectrum of inflammatory cytokines was induced by CVB3 replication via a pathway that requires IL-1 signaling. Our results suggest that IL-1ra may be used as a therapeutic agent to limit inflammation and tissue destruction in myocarditis. |
| Databáze: | OpenAIRE |
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