|
|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: potential for bovine inflammation therapy
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Effects of bovine tumor necrosis factor alpha decoy receptors on cell death and inflammatory cytokine kinetics: potential for bovine inflammation therapy |
| Authors: | Fujisawa, Sotaro Browse this author | | Konnai, Satoru Browse this author →KAKEN DB | | Okagawa, Tomohiro Browse this author | | Maekawa, Naoya Browse this author | | Tanaka, Akina Browse this author | | Suzuki, Yasuhiko Browse this author →KAKEN DB | | Murata, Shiro Browse this author →KAKEN DB | | Ohashi, Kazuhiko Browse this author →KAKEN DB |
| Keywords: | Cattle | | TNF-α | | TNF receptor | | Decoy receptor | | Cell death | | Inflammatory cytokines |
| Issue Date: | 28-Feb-2019 |
| Publisher: | BioMed Central |
| Journal Title: | BMC veterinary research |
| Volume: | 15 |
| Start Page: | 68 |
| Publisher DOI: | 10.1186/s12917-019-1813-0 |
| Abstract: | BackgroundRefractory diseases, including bacterial infections, are causing huge economic losses in dairy farming. Despite efforts to prevent and treat those diseases in cattle, including the use of antimicrobials, it is not well controlled in the field. Several inflammatory cytokines, including tumor necrosis factor alpha (TNF-), play important roles in disease progression; thus, blocking these cytokines can attenuate the acute and sever inflammation and may be a novel strategy for treatment. However, biological drugs targeting inflammatory cytokines have not been used in cattle. Therefore, in this study, bovine sTNFR1 and sTNFR2 IgG1 Fc-fusion proteins (TNFR1-Ig and TNFR2-Ig) were produced, and their anti-inflammatory functions were analyzed in vitro, to develop decoy receptors for bovine TNF-.ResultsBoth TNFR1-Ig and TNFR2-Ig were shown to bind with TNF-, and TNFR2-Ig showed higher affinity toward TNF- than TNFR1-Ig. We next stimulated murine fibroblast-derived cells (L929 cells) with TNF- to induce cell death and analyzed cell viability in the presence of TNFR-Ig proteins. Both TNFR1-Ig and TNFR2-Ig suppressed TNF--induced cell death, significantly improving cell viability. In addition, cell death induced by TNF- was suppressed, even at low TNFR2-Ig concentrations, suggesting TNFR2-Ig has higher activity to suppress TNF- functions than TNFR1-Ig. Finally, to examine TNFR2-Ig's anti-inflammatory, we cultured peripheral blood mononuclear cells from cattle with TNF- in the presence of TNFR2-Ig and analyzed the gene expression and protein production of the inflammatory cytokines IL-1 and TNF-. TNFR2-Ig significantly reduced the gene expression and protein production of these cytokines. Our results suggest that TNFR2-Ig inhibits inflammatory cytokine kinetics by blocking TNF- to transmembrane TNFR, thereby attenuating excessive inflammation induced by TNF-.ConclusionsCollectively, the findings of this study demonstrated the potential of TNFR2-Ig as a novel therapeutic for inflammatory diseases, such as bovine clinical mastitis. Further investigation is required for future clinical application. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/76271 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
|
