Abstract:Objective: To investigate the role of IL35 in the pathogenesis of type 2 diabetes mellitus (T2DM) with carotid atherosclerosis (CAS). Methods: A total of 70 patients with T2DM were enrolled,including 36 patients diagnosed with T2DM without CAS, 34 patients diagnosed with T2DM with CAS, and 35 age, gender and body mass index(BMI) matched healthy control group were enrolled. The expression of P35 mRNA and EBI3 mRNA in peripheral blood mononuclear cells(PBMCs) were detected by realtime quantitative PCR. The concentration of serum IL35 and sVCAM1 were measured using multifunction flow type dot matrix instrument Luminex 200. The model of high glucose stimulated human umbilical vein endothelial cells (HUVECs) was established in vitro, then divided into low glucose(LG) conditions(5 mmol/L glucose), high glucose(HG) conditions (25 mmol/L glucose), high mannitol conditions(25 mmol/L mannitol) and IL35+HG (50 ng/mL IL35+25 mmol/L glucose). The apoptosis rate of HUVECs and the positive rate of VCAM1 in each group were detected by Flow cytometry. Results: Compared to those of control group \[(9.37(3.72-14.55 ng/mL)\], the concentration of serum IL35 were lower in the T2DM alone group\[5.01(2.37-9.87)ng/mL\], and much lower in T2DM with CAS group\[3.92(2.15-6.36)ng/mL\] . Compared to those of control group \[687.4(664.2-832.6)\], the concentration of serum sVCAM1 were higher in the simple T2DM group\[785.2(754.5-938.1)\], and much higher in T2DM with CAS group\[932.4(892.6-1 028.3)\]. Compared to those of control group, the expression of P35 mRNA were lower in the T2DM alone group and T2DM with CAS group. the expression of EBI3 mRNA were similar in all three groups (P>0.05). Compared to those of LG group, The apoptosis rate of HUVECs in HG group were higher after treated with 24 h and 48 h (P<0.05). Compared to those of HG group, the apoptosis rate of HUVECs were lower in IL-35+HG group after treated with 48 h. Compared with LG group, the positive rate of VCAM-1 increased in HG group after 48 h (P<0.05). Compared with HG group, the positive rate of VCAM-1 decreased in IL-35+HG group after 48 h (P<0.05). Conclusion: IL-35 may play a protective role in hyperglycemia-induced endothelial cell injury in vivo and in vitro.
收稿日期: 2018-04-24
基金资助:南京医科大学江苏康达医药卫生科研项目(2017NJMUKD022)
通讯作者:
刘娟利(通讯作者),E-mail:18961911898@163.com
作者简介: 朱静和(1980—),男,主治医师,硕士,主要从事糖尿病血管并发症研究;
引用本文:
朱静和1, 徐昌辉1, 钱雷2, 刘青员1, 蒋凤1, 于建秀2, 刘娟利2. IL-35在2型糖尿病合并颈动脉粥样硬化病变中的作用[J]. 江苏大学学报:医学版, 2018, 28(05): 431-436.
ZHU Jing-he1, XU Chang-hui1, QIAN Lei2, LIU Qing-yuan1, JIANG Feng1, YU Jian-xiu2, LIU Juan-li2. The role of IL-35 in type 2 diabetes mellitus with carotid atherosclerosis
. Journal of Jiangsu University(Medicine Edition), 2018, 28(05): 431-436.
[1]Zhang J, Liu YY, Sun HL, et al. High human cytomegalovirus IgG level is associated with increased incidence of diabetic atherosclerosis in type 2 diabetes mellitus patients\[J\].Med Sci Monit,2015, 21:4102-4210.[2]Apro J, Parini P, Broijersén A, et al. Levels of atherogenic lipoproteins are unexpectedly reduced in interstitial fluid from type 2 diabetes patients\[J\]. J Lipid Res, 2015, 56(8):1633-1639.[3]Tabit CE, Chung WB, Hamburg NM, et al. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications\[J\]. Rev Endocr Metab Disord, 2010, 11(1):61-74.[4]Dixon KO, van der Kooij SW, Vignali DA, et al. Human tolerogenic dendritic cells produce IL35 in the absence of other IL12 family members\[J\]. Eur J Immunol, 2015,45(6):1736-1747.[5]Li X, Fang P, Yang WY, et al. IL35, as a newly proposed homeostasisassociated molecular pattern, plays three major functions including antiinflammatory initiator, effector, and blocker in cardiovascular diseases\[J\]. Cytokine, 2017, S1043-4666 (17):30169-30172.[6]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)\[J\].中华内分泌代谢杂志,2014,30 (10):447-498[7]Kotb NA, Gaber R, Salama M, et al. Clinical and biochemical predictors of increased carotid intimamedia thickness in overweight and obese adolescents with type 2 diabetes\[J\]. Diab Vasc Dis Res, 2012, 9(1):35-41.[8]Sha X,Meng S, Li X,et al. Interleukin35 inhibits endothelial cell activation by suppressing MAPKAP1 pathway\[J\]. J Biol Chem, 2015, 290(31):19307-19318.[9]Collison LW, Vignali DAA. Interleukin35: odd one out or part of the family?\[J\]. Immunol Rev, 2008, 226 (1) :248-262.[10]Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL35 contributes to regulatory Tcell function\[J\]. Nature, 2007, 450 (7169) :566-569.[11]Vignali DA, Kuchroo VK.IL12 family cytokines: immunological playmakers\[J\].Nat Immunol, 2012, 13 (8) :722-726.[12]Fu H,Tang YY,Ouyang XP,et al. Interleukin27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway\[J\]. Biochem Biophys Res Commun,2014, 452(4):881-887.[13]Dorosz SA, Ginolhac A, Kahne T, et al. Role of calprotectin as a modulator of the IL27mediated proinflammatory effect on endothelial cells\[J\]. Mediators Inflamm, 2015, 2015 (3) :1-16.[14]Qiu HN, Liu B, Liu W, et al. Interleukin27 enhances TNFαmediated activation of human coronary artery endothelial cells\[J\]. Mol Cell Biochem,2016, 411(1): 1-10.[15]Rosalinda PS, Nonanzit PH, José Manuel RP, et al. Interleukin27 polymorphisms are associated with premature coronary artery disease and metabolic parameters in the Mexican population: the genetics of atherosclerotic disease (GEA) Mexican study\[J\]. Oncotarget, 2017,8(38):64459-64470.[16]Li Y, Wang Y, Liu Y, et al. The possible role of the novel cytokines IL35 and IL37 in inflammatory bowel disease\[J\]. Mediators Inflamm, 2014, 2014 (7):136329-136339.[17]Cai Z, Wong CK, Kam NW, et al. Aberrant expression of regulatory cytokine IL35 in patients with systemic lupus erythematosus\[J\]. Lupus, 2015, 24 (12):1257-1266.