Peptide-Based TNF-α-Binding Decoy Therapy Mitigates Lipopolysaccharide-Induced Liver Injury in Mice
Abstract
:1. Introduction
2. Results
2.1. Pharmacokinetic Analysis and Tissue Distribution of SEM18 Peptide
2.2. SEM18 Peptide Increases Survival and Decreases Plasma Cytokine Concentrations in Lipopolysaccharide (LPS)-Treated Mice
2.3. SEM18 Peptide Inhibits LPS-Induced Binding of TNF-α to TNFR1 in the Liver
2.4. SEM18 Peptide Mitigates LPS-Induced Liver Injury
2.5. SEM18 Peptide Mitigates LPS-Induced Inflammation and Mitochondrial Injury in the Liver
2.6. SEM18 Peptide Mitigates LPS-Induced Necroptosis and Pyroptosis in the Liver
2.7. SEM18 Peptide Mitigates LPS-Induced Apoptosis and Autophagy Upregulation in the Liver
2.8. Exogenous TNF-α Counteracts the Effects of SEM18 Peptide
3. Discussion
4. Materials and Methods
4.1. Animals and Study Approval
4.2. Peptide Design and Synthesis
4.3. Pharmacokinetic Analysis
4.4. Ex Vivo Bioluminescence Imaging
4.5. Endotoxemia Mouse Model and Peptide Therapy
4.6. Survival Assay
4.7. Liver Tissue Harvesting and Wet/Dry Weight Ratio Assay
4.8. Binding of TNF-α and TNFR1
4.9. Biomarkers and Histological Analysis of Liver Injury
4.10. ELISA
4.11. Immunohistochemistry Staining Assay
4.12. TUNEL Assay
4.13. Immunoblotting Assay
4.14. Transmission Electron Microscopy Analysis
4.15. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Chang, C.-Y.; Hsu, H.-J.; Foo, J.; Shih, H.-J.; Huang, C.-J. Peptide-Based TNF-α-Binding Decoy Therapy Mitigates Lipopolysaccharide-Induced Liver Injury in Mice. Pharmaceuticals 2020, 13, 280. https://doi.org/10.3390/ph13100280
Chang C-Y, Hsu H-J, Foo J, Shih H-J, Huang C-J. Peptide-Based TNF-α-Binding Decoy Therapy Mitigates Lipopolysaccharide-Induced Liver Injury in Mice. Pharmaceuticals. 2020; 13(10):280. https://doi.org/10.3390/ph13100280
Chicago/Turabian StyleChang, Chao-Yuan, Hao-Jen Hsu, Jossen Foo, Hung-Jen Shih, and Chun-Jen Huang. 2020. "Peptide-Based TNF-α-Binding Decoy Therapy Mitigates Lipopolysaccharide-Induced Liver Injury in Mice" Pharmaceuticals 13, no. 10: 280. https://doi.org/10.3390/ph13100280
APA StyleChang, C. -Y., Hsu, H. -J., Foo, J., Shih, H. -J., & Huang, C. -J. (2020). Peptide-Based TNF-α-Binding Decoy Therapy Mitigates Lipopolysaccharide-Induced Liver Injury in Mice. Pharmaceuticals, 13(10), 280. https://doi.org/10.3390/ph13100280