Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe-rentiation

doi:10.7518/hxkq.2017.03.007

Abstract

Abstract:

Objective To explore the therapeutic effect of enhancer of Zeste homolog 2 (EZH2) inhibitor GSK343 on periodontitis by regulating microphage differentiation. Methods Macrophage RAW264.7 cells were divided into the blank (A group), control (B group), lipopolysaccharide (LPS) stimulation (C group), and LPS+GSK343 (D group) groups. Phenotype transformations was determined through Western blot analysis and enzyme-linked immunosorbent assay by detecting the differentiation of phenotypic biological markers, including tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10), and Arginase-1 (Arg-1). Metergasis was identified by performing a phagocytosis test on Esche-richia coli (E. coli). Results Macrophage RAW264.7 cells produced classical phenotypic biomarkers (M1) TNF-α and iNOS under LPS stimulation. The expression levels of IL-10 and Arg-1 increased after adding GSK343 into the culture medium. GSK343 also induced the conversion of M1 macrophages into M2 macrophages. Macrophage RAW264.7 cells exerted a phagocytic effect on E. coli, and this effect was enhanced after adding LPS into the culture medium. GSK343 regulated the macrophage RAW264.7 phagocytosis of E. coli. Conclusion GSK343 possibly participates in the regulation of macrophage differentiation and, consequently, in the latent treatment of periodontitis.

Key words: macrophage, periodontitis, epigenetic, microenvironment

CLC Number:

R 780.2

Zhongchao Wang, Liyuan Fan, Dan Tan, Cong Zhou, Shijun Luo. Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe-rentiation[J]. West China Journal of Stomatology, 2017, 35(3): 264-268.

Figures/Tables 3

References 19

[1]	Chang ZL.Recent development of the mononuclear phago-cyte system: in memory of metchnikoff and ehrlich on the 100th anniversary of the 1908 Nobel Prize in physiology or medicine[J]. Biol Cell, 2009, 101(12):709-721.
[2]	Gordon S, Taylor PR.Monocyte and macrophage hetero-geneity[J]. Nat Rev Immunol, 2005, 5(12):953-964.
[3]	孟焕新. 牙周病学[M]. 北京: 人民卫生出版社, 2012:86-88.
	Meng HX.Periodontology[M]. Beijing: People’s Medical Publishing House, 2012:86-88.
[4]	Vats D, Mukundan L, Odegaard JI, et al.Oxidative metabo-lism and PGC-1beta attenuate macrophage-mediated inflam-mation[J]. Cell Metab, 2006, 4(1):13-24.
[5]	黄秀梨. 微生物学实验指导[M]. 北京: 高等教育出版社, 1999:114-116.
	Huang XL.Microbiological experimental instruction[M]. Beijing: Higher Education Press, 1999:114-116.
[6]	Lumeng CN, Bodzin JL, Saltiel AR.Obesity induces a phe-notypic switch in adipose tissue macrophage polarization[J]. J Clin Invest, 2007, 117(1):175-184.
[7]	Qazi SN, Rees CE, Mellits KH, et al.Development of gfp vectors for expression in listeria monocytogenes and other low G+C gram positive bacteria[J]. Microb Ecol, 2001, 41(4):301-309.
[8]	Lindroth AM, Park YJ.Epigenetic biomarkers: a step for-ward for understanding periodontitis[J]. J Periodontal Im-plant Sci, 2013, 43(3):111-120.
[9]	Gomez RS, Dutra WO, Moreira PR.Epigenetics and perio-dontal disease: future perspectives[J]. Inflamm Res, 2009, 58(10):625-629.
[10]	Stenvinkel P, Karimi M, Johansson S, et al.Impact of in-flammation on epigenetic DNA methylation—a novel risk factor for cardiovascular disease[J]. J Intern Med, 2007, 261(5):488-499.
[11]	Kinane DF, Hart TC.Genes and gene polymorphisms asso-ciated with periodontal disease[J]. Crit Rev Oral Biol Med, 2003, 14(6):430-449.
[12]	Zhang S, Crivello A, Offenbacher S, et al.Interferon-gamma promoter hypomethylation and increased expression in chro-nic periodontitis[J]. J Clin Periodontol, 2010, 37(11):953-961.
[13]	Babel N, Cherepnev G, Babel D, et al.Analysis of tumor necrosis factor-alpha, transforming growth factor-beta, in-terleukin-10, IL-6, and interferon-gamma gene polymorphisms in patients with chronic periodontitis[J]. J Periodontol, 2006, 77(12):1978-1983.
[14]	Zhang S, Barros SP, Moretti AJ, et al.Epigenetic regulation of TNFA expression in periodontal disease[J]. J Periodontol, 2013, 84(11):1606-1616.
[15]	Bonecchi R, Locati M, Mantovani A.Chemokines and can-cer: a fatal attraction[J]. Cancer Cell, 2011, 19(4):434-435.
[16]	刘莹, 高庆, 高艳娥, 等. 宫颈癌中EZH2的表达与细胞增殖和血管生成的关系[J]. 西安交通大学学报(医学版), 2013, 34(5):580-584.
	Liu Y, Gao Q, Gao YE, et al.Expression of EZH2 in cervical cancer and its relationship with cell proliferation angiogenesis[J]. J Xi’an Jiaotong Univ (Med Sci), 2013, 34(5):580-584.
[17]	Alimova I, Venkataraman S, Harris P, et al.Targeting the enhancer of zeste homologue 2 in medulloblastoma[J]. Int J Cancer, 2012, 131(8):1800-1809.
[18]	Kemp CD, Rao M, Xi S, et al.Polycomb repressor complex-2 is a novel target for mesothelioma therapy[J]. Clin Cancer Res, 2012, 18(1):77-90.
[19]	Susol E, Rands AL, Herrick A, et al.Association of markers for TGFbeta3, TGFbeta2 and TIMP1 with systemic sclerosis[J]. Rheumatology (Oxford), 2000, 39(12):1332-1336.