Background
Etanercept is an inhibitor of the inflammatory factor TNF-α and is mainly used for the clinical treatment of rheumatoid arthritis (RA), ankylosing spondylitis, and uveitis [1-3]. Etanercept can competitively inhibit the binding of two subtypes of TNF (TNF-α and TNF-β) to their cell surface receptor (TNFR) and further prevent TNF-α and TNF-β from exerting their biological effects [4].
In vitro, etanercept(20 or 50 μg/mL;7 h) reduced endothelial cell tube formation by inhibiting activation of the NF-κB signaling pathway[7]. The protective effect of etanercept(24h)lies in the restoration of autophagy against TNF-induced endothelial damage in EA.hy926 endothelial cells [5].
Etanercept treatment(0.8 mg/kg/week; 12 weeks;i.p.) significantly restored endothelium-dependent vasorelaxation and resulted in decreased serum levels of TNF-α and increased eNOS expression in rats exposed to CD[6].
参考文献:
[1]. Padilla-Mart EM, Romero SC, et,al. (2019) Drug levels and antibodies against TNF-blockers in spondyloarthritis and rheumatoid arthritis are associated with the activity but they do not predict it. Curr Rheumatol Rev 15:329-335
[2]. D'Adamio S, Silvaggio D, et,al. Pharmacotherapeutic management of psoriasis in adolescents and children. Expert Opin Pharmacother. 2019 Oct;20(14):1777-1785. doi: 10.1080/14656566.2019.1636032. Epub 2019 Jul 4. PMID: 31271541.
[3]. Bartalena L. Commentary: rituximab, adalimumab, etanercept, tocilizumab--are biologics the future for Graves' orbitopathy? Ophthalmic Plast Reconstr Surg. 2014 Sep-Oct;30(5):420-3. doi: 10.1097/IOP.0000000000000221. PMID: 25025391.
[4]. Lim H, Lee SH, et,al. Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis. Int J Mol Sci. 2018 Mar 7;19(3):768. doi: 10.3390/ijms19030768. PMID: 29518978; PMCID: PMC5877629.
[5]. Barbati C, Colasanti T, et,al. Up-regulation of autophagy by etanercept treatment results in TNF-induced apoptosis reduction in EA.hy926 endothelial cell line. Clin Exp Rheumatol. 2021 May-Jun;39(3):606-611. doi: 10.55563/clinexprheumatol/uiqdtq. Epub 2020 Sep 3. PMID: 32896251.
[6]. R?zvan-Valentin S, Güler SA, et,al. Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats. Int J Environ Res Public Health. 2022 Feb 14;19(4):2138. doi: 10.3390/ijerph19042138. PMID: 35206342; PMCID: PMC8872388.
[7]. Yao Y, Cai Y, et,al. Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2021 Mar;259(3):661-671. doi: 10.1007/s00417-020-04956-6. Epub 2020 Oct 12. PMID: 33043386.
Protocol
| Cell experiment [1]: |
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Cell lines
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Human retinal microvascular endothelial cells (HRECs)
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Preparation Method
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Melted Matrigel Matrix was added to a 96-well plate at 100 μL per well and allowed to stand in an incubator (37?橠for 30 min. The HRECs were evenly spread on the Matrigel Matrix on ice. Different concentrations of etanercept or PBS were added to the cells 60 min before the addition of the human recombinant TNF-α (rhTNF-α). The concentration of rhTNF-α was 1 ng/mL and that of etanercept was 20 or 50 μg/mL. The plate was placed at 37?栦or 7 h, cell tube formation images were captured with an inverted microscope (100x).
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Reaction Conditions
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20 or 50 μg/mL;7 h
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Applications
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Etanercept reduces endothelial tube formation.
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| Animal experiment [2]: |
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Animal models
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30 day-old Wistar albino rats(50-70 g)
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Preparation Method
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Rats were separated into the three groups: contro, CD, and CD + ETA (exposed to CD and treated with subcutaneous injections of etanercept (0.8 mg/kg/week) for 12 weeks). The control group was fed with a standard pellet diet. The CD and CD + ETA groups were fed with CD, which is a high-fat diet
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Dosage form
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0.8 mg/kg/week; 12 weeks; s.c.
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Applications
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12-week chronic etanercept treatment significantly restored endothelium-dependent vasorelaxation and resulted in decreased serum levels of TNF-α and increased eNOS expression in rats exposed to CD.
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参考文献:
[1]. Yao Y, Cai Y,et,al. Etanercept as a TNF-alpha inhibitor depresses experimental retinal neovascularization. Graefes Arch Clin Exp Ophthalmol. 2021 Mar;259(3):661-671. doi: 10.1007/s00417-020-04956-6. Epub 2020 Oct 12. PMID: 33043386.
[2].R?zvan-Valentin S, Güler SA,et,al. Etanercept Prevents Endothelial Dysfunction in Cafeteria Diet-Fed Rats. Int J Environ Res Public Health. 2022 Feb 14;19(4):2138. doi: 10.3390/ijerph19042138. PMID: 35206342; PMCID: PMC8872388.
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