乳酸/乳酸化修饰调控巨噬细胞参与牙周病发生的研究进展

doi:10.13701/j.cnki.kqyxyj.2024.07.002

摘要/Abstract

摘要： 乳酸作为糖酵解的最终产物,在能量来源、信号分子和免疫调节方面具有重要的作用,同时也是炎症性疾病的标志物之一。乳酸化修饰是近年来新发现的一种以乳酸和赖氨酸残基为底物的蛋白质翻译后修饰方式,其与多种炎性疾病密切相关。牙周炎是一种由牙周致病菌引发的免疫炎症,宿主免疫反应引发牙周组织损伤是其重要病因。最新研究发现,牙周炎微环境中乳酸含量增加,导致乳酸化水平的上升,最终可通过影响巨噬细胞极化和促进成骨细胞分化来抑制炎症进展和促进组织修复。因此,本文对近年有关乳酸/乳酸化修饰调控巨噬细胞功能及在牙周炎等炎性疾病中的研究进展进行了总结,以期为牙周炎的研究及治疗提供参考。

关键词: 乳酸, 乳酸化修饰, 牙周炎, 免疫炎症, 蛋白质翻译后修饰

Abstract: Lactate, as the end product of glycolysis, plays an important role in terms of energy sources, signaling molecules, and immune adjustment. Lactylation (Kla) is a newly discovered method to translate proteins based on lactate and lithium acid residues that are closely associated with a variety of inflammatory diseases. Peritoneal pathogens are the main cause of periodontitis (PD), which is an immune inflammation caused by the host's immune response. According to recent research, the increase of lactate content in periodontitis microenvironment leads to the increase of lactylation level, which can eventually slow down the spread of inflammation and help tissue repair by changing the polarization of macrophages and promoting the differentiation of bone cell. Therefore, this paper reviews the research progress of lactate/lactylation in regulating macrophage function and inflammatory diseases such as periodontitis in recent years, so as to provide reference for follow-up research and treatment of periodontitis.

Key words: lactate, lactylation, periodontitis, immune inflammation, post-translational modifications

韦艳, 田艾. 乳酸/乳酸化修饰调控巨噬细胞参与牙周病发生的研究进展[J]. 口腔医学研究, 2024, 40(7): 578-582.

WEI Yan, TIAN Ai. Research Progress on Regulation of Macrophages Involvement in Periodontal Disease by Lactate/Lactation Modification[J]. Journal of Oral Science Research, 2024, 40(7): 578-582.

参考文献

[1] Jin N, Bi A, Lan X, et al. Identification of metabolic vulnerabilities of receptor tyrosine kinases-driven cancer [J]. Nat Commun, 2019, 10(1):2701.
[2] Tang F, Lane S, Korsak A, et al. Lactate-mediated glia-neuronal signalling in the mammalian brain [J]. Nat Commun, 2014, 5:3284.
[3] Colegio OR, Chu NQ, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid [J]. Nature, 2014, 513(7519):559-563.
[4] Souto-Carneiro MM, Klika KD, Abreu MT, et al. Effect of increased lactate dehydrogenase A activity and aerobic glycolysis on the proinflammatory profile of autoimmune CD8⁺ T cells in rheumatoid arthritis [J]. Arthritis Rheumatol, 2020, 72(12):2050-2064.
[5] Zhang M, Lu N, Guo XY, et al. Influences of the lncRNA TUG1-miRNA-34a-5p network on fibroblast-like synoviocytes (FLSs) dysfunction in rheumatoid arthritis through targeting the lactate dehydrogenase A (LDHA) [J]. J Clin Lab Anal, 2021, 35(9):e23969.
[6] Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation [J]. Nature, 2019, 574(7779):575-580.
[7] Zhang N, Jiang N, Yu L, et al. Protein lactylation critically regulates energy metabolism in the protozoan parasite Trypanosoma brucei [J]. Front Cell Dev Biol, 2021, 9:719720.
[8] D'Aiuto F, Gkranias N, Bhowruth D, et al. Systemic effects of periodontitis treatment in patients with type 2 diabetes: a 12 month, single-centre, investigator-masked, randomised trial published correction appears in Lancet Diabetes Endocrinol [J]. Lancet Diabetes Endocrinol, 2018, 6(12):954-965.
[9] Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 [J]. Lancet, 2015, 386(9995):743-800.
[10] Buset SL, Walter C, Friedmann A, et al. Are periodontal diseases really silent? A systematic review of their effect on quality of life [J]. J Clin Periodontol, 2016, 43(4):333-344.
[11] Kvacskay P, Yao N, Schnotz JH, et al. Increase of aerobic glycolysis mediated by activated T helper cells drives synovial fibroblasts towards an inflammatory phenotype: new targets for therapy? [J]. Arthritis Res Ther, 2021, 23(1):56.
[12] Yang B, Pang X, Li Z, et al. Immunomodulation in the treatment of periodontitis: Progress and perspectives [J]. Front Immunol, 2021, 12:781378.
[13] Brito F, Curcio HFQ, da Silva Fidalgo TK. Periodontal disease metabolomics signatures from different biofluids: a systematic review [J]. Metabolomics, 2022, 18(11):83.
[14] Liu X, Wang J, Lao M, et al. Study on the effect of protein lysine lactylation modification in macrophages on inhibiting periodontitis in rats [J]. J Periodontol, 2024, 95(1):50-63.
[15] Manosalva C, Quiroga J, Hidalgo AI, et al. Role of lactate in inflammatory processes: Friend or foe [J]. Front Immunol, 2022, 12:808799.
[16] Pucino V, Bombardieri M, Pitzalis C, et al. Lactate at the crossroads of metabolism, inflammation, and autoimmunity [J]. Eur J Immunol, 2017, 47(1):14-21.
[17] Levitt MD, Levitt DG. Quantitative evaluation of D-lactate pathophysiology: New insights into the mechanisms involved and the many areas in need of further investigation [J]. Clin Exp Gastroenterol, 2020, 13:321-337.
[18] Ippolito L, Morandi A, Giannoni E, et al. Lactate: A metabolic driver in the tumour landscape [J]. Trends Biochem Sci, 2019, 44(2):153-166.
[19] Brooks GA, Curl CC, Leija RG, et al. Tracing the lactate shuttle to the mitochondrial reticulum [J]. Exp Mol Med, 2022, 54(9):1332-1347.
[20] Brooks GA. What the lactate shuttle means for sports nutrition [J]. Nutrients, 2023, 15(9):2178.
[21] Rubin RP. Carl and gerty cori: A collaboration that changed the face of biochemistry [J]. J Med Biogr, 2021, 29(3):143-148.
[22] Ishikawa T, Sasaki D, Aizawa R, et al. The role of lactic acid on wound healing, cell growth, cell cycle kinetics, and gene expression of cultured junctional epithelium cells in the pathophysiology of periodontal disease [J]. Pathogens, 2021, 10(11):1507.
[23] Stehle HW, Leblebicioglu B, Walters JD. Short-chain carboxylic acids produced by gram-negative anaerobic bacteria can accelerate or delay polymorphonuclear leukocyte apoptosis in vitro [J]. J Periodontol, 2001, 72(8):1059-1063.
[24] Hui S, Ghergurovich JM, Morscher RJ, et al. Glucose feeds the TCA cycle via circulating lactate [J]. Nature, 2017, 551(7678):115-118.
[25] Qiqiang L, Huanxin M, Xuejun G. Longitudinal study of volatile fatty acids in the gingival crevicular fluid of patients with periodontitis before and after nonsurgical therapy [J]. J Periodontal Res, 2012, 47(6):740-749.
[26] Niederman R, Zhang J, Kashket S. Short-chain carboxylic-acid-stimulated, PMN-mediated gingival inflammation [J]. Crit Rev Oral Biol Med, 1997, 8(3):269-290.
[27] Luo Y, Gou H, Chen X, et al. Lactate inhibits osteogenic differentiation of human periodontal ligament stem cells via autophagy through the MCT1-mTOR signaling pathway [J]. Bone, 2022, 162:116444.
[28] Wu Y, Wang M, Feng H, et al. Lactate induces osteoblast differentiation by stabilization of HIF1α [J]. Mol Cell Endocrinol, 2017, 452:84-92.
[29] Yang K, Fan M, Wang X, et al. Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis [J]. Cell Death Differ, 2022, 29(1):133-146.
[30] Wang J, Yang P, Yu T, et al. Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages [J]. Int J Biol Sci, 2022, 18(16):6210-6225.
[31] Meng X, Baine JM, Yan T, et al. Comprehensive analysis of lysine lactylation in rice (Oryza sativa) grains [J]. J Agric Food Chem, 2021, 69(29):8287-8297.
[32] Li L, Chen K, Wang T, et al. Author correction: Glis1 facilitates induction of pluripotency via an epigenome-metabolome-epigenome signalling cascade [J]. Nat Metab, 2020, 2(10):1179.
[33] Irizarry-Caro RA, McDaniel MM, Overcast GR, et al. TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation [J]. Proc Natl Acad Sci U S A, 2020, 117(48):30628-30638.
[34] Hagihara H, Shoji H, Otabi H, et al. Protein lactylation induced by neural excitation [J]. Cell Rep, 2021, 37(2):109820.
[35] Nango H, Ohtani M. S-1-propenyl-L-cysteine suppresses lipopolysaccharide-induced expression of matrix metalloproteinase-1 through inhibition of tumor necrosis factor-α converting enzyme-epidermal growth factor receptor axis in human gingival fibroblasts [J]. PLoS One, 2023, 18(4):e0284713.
[36] Hayata M, Watanabe N, Kamio N, et al. Cynaropicrin from cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells [J]. J Nat Med, 2019, 73(1):114-123.
[37] Viola A, Munari F, Sánchez-Rodríguez R, et al. The metabolic signature of macrophage responses [J]. Front Immunol, 2019, 10:1462.
[38] Sun S, Xu X, Liang L, et al. Lactic acid-producing probiotic saccharomyces cerevisiae attenuates ulcerative colitis via suppressing macrophage pyroptosis and modulating gut microbiota [J]. Front Immunol, 2021, 12:777665.
[39] Gruber R. Osteoimmunology: Inflammatory osteolysis and regeneration of the alveolar bone [J]. J Clin Periodontol, 2019, 46 Suppl 21:52-69.
[40] Nian F, Qian Y, Xu F, et al. LDHA promotes osteoblast differentiation through histone lactylation [J]. Biochem Biophys Res Commun, 2022, 615:31-35.