Involvement of Toll-like receptor 4 in vinorelbine-induced vascular endothelial injury

Qian,Weiwei; Gao,Liyan; Chen,Chong; Tan,Yingchun; Zhou,Ying; Li,Zhenyu

doi:10.3892/etm.2015.2494

July-2015 Volume 10 Issue 1

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July-2015 Volume 10 Issue 1

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Involvement of Toll-like receptor 4 in vinorelbine-induced vascular endothelial injury

Authors:
- Weiwei Qian
- Liyan Gao
- Chong Chen
- Yingchun Tan
- Ying Zhou
- Zhenyu Li
View Affiliations / Copyright

Affiliations: Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, School of Nursing, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China

Copyright: © Qian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 62-66
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Published online on: May 14, 2015

https://doi.org/10.3892/etm.2015.2494
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Abstract

Vinorelbine (VIN) is a semi-synthetic vinca alkaloid and is one of the most active agents for the treatment of solid tumors. The drug is commonly administered through a peripheral vein. Although VIN is known to cause local venous toxicity, such as drug‑induced phlebitis, the mechanism responsible for the toxicity remains unclear. To investigate the role of Toll‑like receptor 4 (TLR4) in VIN‑induced vascular endothelial injury, human umbilical vein endothelial cells (HUVECs) were prepared from umbilical cords recovered with the written informed consent of the parents and treated with VIN for 60 min. Following the washing away of the VIN, the cells were cultured for a further 6 and 12 h, and the changes in TLR4 expression in the HUVECs were detected by quantitative polymerase chain reaction and western blot analyses. Finally, the effects of VIN on the translocation of nuclear factor κB (NF‑κB) were determined by immunofluorescence and confocal analysis. The VIN‑treated cells were stretched, extended and irregular while the control cells exhibited normal morphology. The TLR4 mRNA and protein levels were significantly higher in the VIN‑treated HUVECs than those in the control group (P<0.05). The rate of NF‑κB p65 nuclear translocation in the VIN‑treated HUVECs was significantly higher than that in the vehicle‑treated group (P<0.05). These results indicated that TLR4 is involved in the development of VIN‑induced vascular endothelial injury by affecting the translocation of NF-κB.

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1	Potier P: The synthesis of Navelbine prototype of a new series of vinblastine derivatives. Semin Oncol. 16:(2 Suppl 4). 2–4. 1989.PubMed/NCBI
2	Depierre A, Lemarie E, Dabouis G, et al: A phase II study of Navelbine (vinorelbine) in the treatment of non-small-cell lung cancer. Am J Clin Oncol. 14:115–119. 1991. View Article : Google Scholar : PubMed/NCBI
3	Fumoleau P, Delgado FM, Delozier T, et al: Phase II trial of weekly intravenous vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol. 11:1245–1252. 1993.PubMed/NCBI
4	Devizzi L, Santoro A, Bonfante V, et al: Vinorelbine: a new promising drug in Hodgkin's disease. Leuk Lymphoma. 22:409–414. 1996. View Article : Google Scholar : PubMed/NCBI
5	Yoh K, Niho S, Goto K, et al: High body mass index correlates with increased risk of venous irritation by vinorelbine infusion. J Clin Oncol. 34:206–209. 2004.
6	Yoh K, Niho S, Goto K, et al: Randomized trial of drip infusion versus bolus injection of vinorelbine for the control of local venous toxicity. Lung Cancer. 55:337–341. 2007. View Article : Google Scholar : PubMed/NCBI
7	Lewis GB and Hecker JF: Infusion thrombophlebitis. Br J Anaesth. 57:220–233. 1985. View Article : Google Scholar : PubMed/NCBI
8	Falchuk KH, Peterson L and McNeil BJ: Microparticulate-induced phlebitis. Its prevention by in-line filtration. N Engl J Med. 312:78–82. 1985. View Article : Google Scholar : PubMed/NCBI
9	Miyake K: Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol. 19:3–10. 2007. View Article : Google Scholar : PubMed/NCBI
10	Ohashi K, Burkart V, Flohé S and Kolb H: Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol. 164:558–561. 2000. View Article : Google Scholar : PubMed/NCBI
11	Vabulas RM, Braedel S, Hilf N, et al: The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. J Biol Chem. 277:20847–20853. 2002. View Article : Google Scholar : PubMed/NCBI
12	Roelofs MF, Boelens WC, Joosten LA, et al: Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol. 176:7021–7027. 2006. View Article : Google Scholar : PubMed/NCBI
13	Guillot L, Balloy V, McCormack FX, et al: Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4. J Immunol. 168:5989–5992. 2002. View Article : Google Scholar : PubMed/NCBI
14	Rakoff-Nahoum S and Medzhitov R: Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science. 317:124–127. 2007. View Article : Google Scholar : PubMed/NCBI
15	Park JS, Svetkauskaite D, He Q, et al: Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem. 279:7370–7377. 2004. View Article : Google Scholar : PubMed/NCBI
16	Kawai T and Akira S: TLR signaling. Semin Immunol. 19:24–32. 2007. View Article : Google Scholar : PubMed/NCBI
17	Tricot O, Mallat Z, Heymes C, et al: Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation. 101:2450–2453. 2000. View Article : Google Scholar : PubMed/NCBI
18	Scarabelli TM, Stephanou A, Pasini E, et al: Different signaling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischemia/reperfusion injury. Circ Res. 90:745–748. 2002. View Article : Google Scholar : PubMed/NCBI
19	Bannerman DD and Goldblum SE: Mechanisms of bacterial lipopolysaccharide induced endothelial apoptosis. Am J Physiol Lung Cell Mol Physiol. 284:L899–L914. 2003. View Article : Google Scholar : PubMed/NCBI
20	Frantz S, Kobzik L, Kim YD, et al: Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest. 104:271–280. 1999. View Article : Google Scholar : PubMed/NCBI
21	Faure E, Equils O, Sieling PA, et al: Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 275:11058–11063. 2000. View Article : Google Scholar : PubMed/NCBI
22	Faure E, Thomas L, Xu H, et al: Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. J Immunol. 166:2018–2024. 2001. View Article : Google Scholar : PubMed/NCBI
23	Barnes PJ and Karin M: Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 336:1066–1071. 1997. View Article : Google Scholar : PubMed/NCBI
24	Winn RK and Harlan JM: The role of endothelial cell apoptosis in inflammatory and immune diseases. J Thromb Haemost. 3:1815–1824. 2005. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Involvement of Toll-like receptor 4 in vinorelbine-induced vascular endothelial injury

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