The influence of selective COX-2 inhibitor on phase of healing surgical wounds: proliferation and secretion of bFGF by endothelial cells
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The process of wound healing consists of the following phases: inflammation, proliferation, remodeling. Non-steroidal antiinflammatory drugs may be important in this process, especially in a stage called angiogenesis. For this reason, it was decided to investigate the effect of selective COX-2 (cyclooxygenase 2) inhibitor (NS-398) on the proliferation of endothelial cells and their ability to secrete bFGF (fibroblast growth factor) for vascular endothelial cells (HMEC-1). For determination of the secretion of bFGF in a cell line HMEC-1 immunosorbent ELISA assays were used. In turn, the cell proliferation assay was performed using the MTT method. Using MTT method, it was found that NS-398 at 10 μM did not affect cell viability. Whereas selective COX-2 inhibitor at 100 μM decreased cell viability in a statistically significant manner and inhibited the proliferative effect of 100 μg/mL LPS at concentrations of 10 and 100 μM. In the further step, application of NS-398 (10 and 100 μM) with LPS (100 μg/mL; inflammatory environment) reduced the secretion of bFGF in a statistically significant manner. The investigations showed that NS-398 has an antiangiogenic effect which is based on reducing the proliferation of vascular endothelial cells and inhibiting the secretion of bFGF- factor responsible for angiogenesis during wound healing.
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- Ades E.W., Candal F.J., Swerlick R.A., George V.G., Summers S., Bosse D.C., Lawley T.J. 1992. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J. Invest. Dermatol. 99: 683–690.
- Akarasereenont P., Bakhle Y.S., Thiemermann C., Vane J.R. 1995. Cytokine-mediated induction of cyclo-oxygenase-2 by activation of tyrosine kinase in bovine endothelial cells stimulated by bacterial lipopolysaccharide. Br. J. Pharmacol. 115: 401–408.
- Akarasereenont P., Mitchell J.A., Thiemermann C., Vane J.R. 1994. Involvement of tyrosine kinase in the induction of cyclo-oxygenase and nitric oxidase synthase by endotoxin in cultured cells. Br. J. Pharmacol. 113: 1522–1528.
- Akino K., Hirano A. 2013. Basic fibroblast growth factor in scarless wound healing. Adv. Wound Care. 2: 44–49.
- Boonmasawai S., Akarasereenont P., Techatraisak K., Thaworn A. Chotewuttakorn, S., Palo T., 2009. Effects of selective COX-inhibitors and classical NSAIDs on endothelial cell proliferation and migration induced by human cholangiocarcinoma cell culture. J. Med. Assoc. Thai. 92: 1508–1515.
- Fairweather M., Heit Y.I., Buie J., Rosenberg L.M., Briggs A., Orgill D.P., Bertagnolli M.M. 2015. Celecoxib inhibits early cutaneous wound healing. J. Surg. Res. 194(2): 717–724.
- Flis S., Soltysiak-Pawluczuk D., Jedrych A., Jastrzebski Z., Remiszewska M., Splawinski J. 2006. Antiangiogenic effect of sulindac sulfide could be secondary to induction of apoptosis and cell cycle arrest. Anticancer Res. 26: 3033–3042.
- Geusens P., Emans P.J., de Jong J.J., van den Bergh J. 2013. NSAIDs and fracture healing. Curr. Opin. Rheumatol. 25(4): 524–531.
- Goren I., Lee S.Y., Maucher D., Nüsing R., Schlich T., Pfeilschifter J., Frank S. 2017. Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds. Int. Wound J. 14(1): 53–63.
- Matsuhita K., Motani R., Sakuta T., Nagaoka S., Matsuyama T., Abeyama K., Maruyama I., Takada H., Torii M. 1999. Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture. Infect. Immun. 67: 1633–1639.
- Niederburger E., Manderscheid C., Grosch S., Schmidt H., Ehnert C., Geisslinger G. 2004. Effects of selective COX-2 inhibitors celecoxib and rofecoxib on human vascular cells. Biochem. Pharmacol. 68: 341–50.
- Piao Y.L., Seo S.Y., Lim S.C., Cho H. 2014. Wound healing effects of new 15-hydroxyprostaglandin dehydrogenase inhibitors. Prostaglandins Leukot. Essent. Fatty Acids. 91(6): 325-332.
- Reinke J.M., Sorg H. Wound repair and regeneration. 2012. Eur. Surg. Res. 49(1): 35–43.
- Vane J.R., Botting R.M. 1998. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 47: 78–87.
- Wiktorowska-Owczarek A. 2013. The effect of valdecoxib on the production of growth factors evoked by hypoxia and bacterial lipopolysaccharide in HMEC-1 cells. Adv. Clin. Exp. Med. 22: 795–800.
- Wiktorowska-Owczarek A. 2014. The effect of diclofenac on proliferation and production of growth factors by endothelial cells (HMEC-1) under hypoxia and inflammatory conditions. Acta Pharm. 64: 131–138.
- Wiktorowska-Owczarek A., Jóźwiak-Bębenista M., Nowak J.Z. 2011. Effects of hypoxia on cyclic AMP signaling and VEGF/bFGF generation in different types of cultured cells. Pharmacol. Rep. 63: 574–575.
- Wiktorowska-Owczarek A., Namiecińska M., Owczarek J. 2015. The effect of ibuprofen on bFGF, VEGF secretion and cell proliferation in the presence of LPS in HMEC-1 cells. Acta Pol. Pharm. 72(5): 889–894.
- Woods J.M., Mogollon A., Amin M.A., Martinez R.J., Koch A.E. 2003. The role of COX-2 in angiogenesis and rheumatoid arthritis. Exp. Mol. Pathol. 74: 282–290.
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