TNFR-Fc fusion protein expressed by in vivo electroporation improves survival rates and myocardial injury in coxsackievirus induced murine myocarditis

Biochemical and Biophysical Research Communications
Jong-Mook KimEun-Seok Jeon

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is one of the major cytokines that modulate the immune response in viral myocarditis, but its role has not yet been thoroughly evaluated. We antagonized TNF-alpha using the expressed soluble p75 TNF receptor linked to the Fc portion of the human IgG1 gene (sTNFR:Fc) by in vivo electroporation, and evaluated its effects on experimental coxsackieviral B3 (CVB3) myocarditis. A plasmid DNA encoding sTNFR:Fc (15microg/mouse) was injected into the gastrocnemius muscles of Balb/C male mice followed by electroporation (day -1). Control mice were injected with an empty vector. One day after electroporation, mice were infected with CVB3 (day 0). Serum levels of sTNFR:Fc increased from day 2 and peaked at day 5 following electroporation. The heart virus titers of sTNFR:Fc mice were higher than those of controls at day 3. However, subsequent to day 12, the survival rates of the sTNFR:Fc mice were significantly higher than those of the controls (36% versus 0% at day 27, P<0.01). Histopathological examination indicated that inflammation and myocardial fibrosis were significantly decreased in sTNFR:Fc mice at day 12. The expressed sTNFR:Fc could modulate the inflammatory process during the post-viremic ...Continue Reading

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Citations

Nov 26, 2010·The Journal of Membrane Biology·Oksana DyachokTerence F McDonald
Dec 3, 2014·International Journal of Cardiology·Chandirasegaran MassilamanyJay Reddy
Feb 6, 2016·Circulation Research·Gabriel FungBruce McManus
Oct 3, 2014·Biological & Pharmaceutical Bulletin·Byung-Kwan Lim, Jin Hee Kim
Apr 30, 2020·International Journal of Molecular Sciences·Soo-Hyeon YunEun-Seok Jeon
Feb 18, 2021·Journal of Basic and Clinical Physiology and Pharmacology·Manal A IbrahimRasha N Mohammed
Feb 6, 2020·Recent Patents on Inflammation & Allergy Drug Discovery·Ronald C M FungAlexander K C Leung

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