The immunosuppressive effect of sinomenine on lymphocytes stimulated by allogeneic islets

doi:10.3877/cma.j.issn.1674-3903.2018.03.003

Abstract

Abstract:

Objective

To investigate the immunosuppressive effect of sinomenine (SIN) on the lymphocytes stimulated by allogeneic islets and the influence on activity and function of islets.

Methods

Isolated islets from Wistar rats as the stimulus and lymphocytes from spleen of Lewis rats as the reactive cells were cocultured in vitro, and then divided into 4 groups: SIN group with SIN, islets and lymphocytes cocultured; Tac (tacrolimus) group with Tac, islets and lymphocytes cocultured; negative control group with islets and lymphocytes cocultured; blank control group with lymphocyte cultured alone.The concentration of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-10 and insulin in the supernatant were detected by enzyme-linked immunosorbent assay, the proliferation of lymphocytes was measured by methyl thiazolyl tetrazolium assay, and the activity of islet cells was tested by acridine orange and propidium iodide staining.

Results

On the 3th days after cocultured, the proliferation rates of lymphocytes in the SIN group and Tac group were (33.9±2.8)% and (33.2±3.0)% respectively, both lower than that in the negative control group (P all <0.05), but there was no statistical difference between the SIN group and Tac group (P>0.05). The concentration of IFN-γ and IL-2 in the SIN group were (67±6) and (322±21) pg/mL respectively, both lower than those in the negative control group and higher than those in the blank control group (P all <0.05), but no statistical difference compared with the Tac group (P>0.05). The supernatant concentration of IL-10 in the SIN group was (76±4) pg/mL, and higher than those in the other 3 groups (P all <0.05). The insulin stimulation index and activity of islets in the SIN group were (1.73±0.24) and (82.5±4.7)% respectively, both superior to those in the Tac group and the negative control group (P all <0.05).

Conclusions

SIN not only had immunosuppressive effect on lymphocytes stimulated by allogeneic islets, but also could alleviate the immune injury to the islets. What′s more, it could maintain the activity and insulin secretion function of islet cells better compared with Tac.

Key words: Sinomenine, Islets, Immunosuppressive, Lymphocytes

Zizhao Jiao, Maozhu An, Haixia Fu, Yang Li, Fenglou Li, Lianfen Sheng. The immunosuppressive effect of sinomenine on lymphocytes stimulated by allogeneic islets[J]. Chinese Journal of Transplantation(Electronic Edition), 2018, 12(03): 106-110.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhyzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-3903.2018.03.003

https://zhyzzz.cma-cmc.com.cn/EN/Y2018/V12/I03/106

Figures/Tables 3

References 23

1	Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen[J]. N Engl J Med, 2000，343(4):230-238.
2	Azzi J, Geara AS, El-Sayegh S, et al. Immunological aspects of pancreatic islet cell transplantation[J]. Expert Rev Clin Immunol, 2010，6(1):111-124.
3	Ricordi C, Strom TB. Clinical islet transplantation: advances and immunological challenges[J]. Nat Rev Immunol, 2004，4(4):259-268.
4	孙世芹，王有志，周亚斌. 中药单体化合物免疫抑制活性的研究进展[J]. 中国中药杂志，2010，35(3):393-396.
5	秦峰，蔡辉. 青藤碱药理作用研究进展[J]. 现代中药研究与实践，2016，30(4):81-86.
6	黎炼，罗志刚. 青藤碱的免疫抑制作用机制的研究进展[J]. 中南医学科学杂志，2015，43(1):86-89.
7	Feng H, Yamaki K, Takano H, et al. Suppression of Th1 and Th2 immune responses in mice by sinomenine, an alkaloid extracted from the chinese medicinal plant sinomenium acutum[J]. Planta Med, 2006，72(15):1383-1388.
8	Chen Z, Tao ZZ, Zhou XH, et al. Immunosuppressive effect of sinomenine in an allergic rhinitis mouse model[J]. Exp Ther Med, 2017，13(5):2405-2410.
9	Cheng Y, Zhang J, Hou W, et al. Immunoregulatory effects of sinomenine on the T-bet/GATA-3 ratio and Th1/Th2 cytokine balance in the treatment of mesangial proliferative nephritis[J]. Int Immunopharmacol, 2009，9(7-8):894-899.
10	Qin T, Du R, Huang F, et al. Sinomenine activation of Nrf2 signaling prevents hyperactive inflammation and kidney injury in a mouse model of obstructive nephropathy[J]. Free Radic Biol Med, 2016，92:90-99.
11	Zhao Z, Guan R, Song S, et al. Sinomenine protects mice against ischemia reperfusion induced renal injury by attenuating inflammatory response and tubular cell apoptosis[J]. Int J Clin Exp Pathol, 2013，6(9):1702-1712.
12	Lacy PE. Pancreatic islet cell transplant[J]. Mt Sinai J Med, 1994，61(1):23-31.
13	王玉生，黄江波. 中药在移植免疫中的研究进展[J]. 中国医药指南，2013，11(26):56-57.
14	王有志，李春荣，莫志贤. 青风藤化学成分与药理研究进展[J]. 医药导报，2004，23(3):185-187.
15	Shu L, Yin W, Zhang J, et al. Sinomenine inhibits primary CD4^＋ T-cell proliferation via apoptosis[J]. Cell Biol Int, 2007，31(8):784-789.
16	Li L, Luo Z, Song Z, et al. Pre-transplant infusion of donor-derived dendritic cells maintained at the immature stage by sinomenine increases splenic Foxp3^＋ Tregs in recipient rats after renal allotransplantation[J]. Transpl Immunol, 2017，45:22-28.
17	杨庞，杨罗艳，罗志刚. 青藤碱对肾移植大鼠T细胞亚群的影响[J]. 临床泌尿外科杂志，2003，18(10):620-622.
18	王毅，钱坤，罗志刚，等. 青藤碱对人外周血CD4^＋ T淋巴细胞增殖和细胞内Ca^2＋浓度影响的体外研究[J/CD]. 中华细胞与干细胞杂志：电子版，2011，1(2):34-36.
19	蔡振刚，于志军，温爽，等. 青藤碱对大鼠肝移植急性排斥反应的影响[J]. 辽宁中医药大学学报，2010，12(4):112-114.
20	Millán O, Rafael-Valdivia L, San Segundo D, et al. Should IFN-γ，IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study[J]. Clin Immunol, 2014，154(2):141-154.
21	Millán O, Rafael-Valdivia L, Torrademé E, et al. Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients[J]. Cytokine, 2013，61(2):556-564.
22	Mulligan MS, Warner RL, McDuffie JE, et al. Regulatory role of Th-2 cytokines, IL-10 and IL-4, in cardiac allograft rejection[J]. Exp Mol Pathol, 2000，69(1):1-9.
23	Qin T, Du R, Huang F, et al. Sinomenine activation of Nrf2 signaling prevents hyperactive inflammation and kidney injury in a mouse model of obstructive nephropathy[J]. Free Radic Biol Med, 2016，92:90-99.

组别	IFN-γ	IL-2	IL-10
SIN组	67±6	322±21	76±4
Tac组	63±6	307±20	51±5^a
阴性对照组	128±8^a	572±15^a	42±4^a
空白对照组	42±5^a	194±12^a	36±5^a

组别	IFN-γ	IL-2	IL-10
SIN组	67±6	322±21	76±4
Tac组	63±6	307±20	51±5^a
阴性对照组	128±8^a	572±15^a	42±4^a
空白对照组	42±5^a	194±12^a	36±5^a

组别	胰岛素分泌量(mU/L)		胰岛素刺激指数
组别	高糖	低糖	胰岛素刺激指数
SIN组	14.7±2.1	8.3±1.2	1.73±0.24
Tac组	11.8±1.8^a	7.7±1.2^a	1.49±0.17^a
阴性对照组	6.8±1.0^a	5.7±0.8^a	1.18±0.12^a

组别	胰岛素分泌量(mU/L)		胰岛素刺激指数
组别	高糖	低糖	胰岛素刺激指数
SIN组	14.7±2.1	8.3±1.2	1.73±0.24
Tac组	11.8±1.8^a	7.7±1.2^a	1.49±0.17^a
阴性对照组	6.8±1.0^a	5.7±0.8^a	1.18±0.12^a

[1]	Yaping Wang, Jing Fan, Niuniu Hou, Rui Ling. Clinical significance of tumor-infiltrating lymphocytes in HER-2-positive early breast cancer [J]. Chinese Journal of Breast Disease(Electronic Edition), 2023, 17(04): 203-209.
[2]	Chen Luo, Kaican Zong, Shiying Li, Yingya Fu. MicroRNA-199a-3p participates in the immune response after Mycoplasma pneumoniae infection in children by regulating the expression of CD4⁺ T cells [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 569-574.
[3]	Minrong Ma, Cong Li, Qin Zhou. Current research status of treatment of cervical cancer [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(05): 497-504.
[4]	Chunying Han, Tingting Wang, Yanyan Li, Jinxia Piao. Current research status on predictors of lymphatic vascular invasion in patients with endometrial carcinoma [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 403-409.
[5]	Ouchan Hu, Zhongying Huang. Current status and outlook of research in treatment of unexplained recurrent spontaneous abortion [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(01): 16-22.
[6]	Xiaofang Zhang, Ping Wang. Research progress on diagnosis and therapy for vaginal melanoma [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2022, 18(06): 621-626.
[7]	Rui Yuan, Wenjia Hu, Xien Gui, Yajun Yan, Ling Feng, Hengning Ke, Yong Xiong, Rongrong Yang. Application of refined lymphocyte subsets detection on patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(02): 84-91.
[8]	Yang Fan, Guoli Li, Yu Hao, Yu Cao, Fangyuan Li, Zengtao Wang, Hui Zeng. Dynamic recovery of splenic T lymphocytes function in mice with endotoxin-induced sepsis [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(01): 32-40.
[9]	Jian Cui, Qing Dai. The relationship between the proportion of Treg cells and anaphylaxis was studied based on anaphylaxis model induced by hepatic cystic echinococcosis [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(04): 427-430.
[10]	Yuan Zhang, Xiaolong Li, Yapeng Wang. Relationship between ANGPTL2 protein and immunosuppressive cell infiltration in pancreatic cancer and its clinical significance [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(02): 145-148.
[11]	Kechun Chen, Qiuyi Wu, Jian Li, Yin Zhou, Zhou Xu. Relationship between the first CT signs after mechanical thrombectomy and prognosis of patients based on different neutrophil-lymphocyte ratios [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2023, 13(04): 215-221.
[12]	Meisha Fu, Yuhua Zhou, Hui Li, Chunyan Xue. Effect of lymphocyte immunotherapy on T lymphocyte subset distribution and PD1/PD-L1 expression in patients with recurrent miscarriage [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(06): 726-730.
[13]	Wenbo Niu, Fengpeng Wu, Yueping Liu, Chaoxi Zhou, Juan Zhang, Xuhua Hu, Baokun Li, Gueying Wang. Neoadjuvant chemoradiotherapy for treatment of locally advanced rectal cancer: Efficacy and tumor immune microenvironment changes [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(05): 519-523.
[14]	Yi Liu, Min Pan, Yao Chen. Rupatadine combined with ebastine for treatment of chronic urticaria: efficacy and impact on complement level and T lymphocytes [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(02): 189-194.
[15]	Ru Fan, Yuqing Liu, Xiaorong Hu, Yiqi Wang, Fen Zhang, Xing Cen, Yujie Bu, Junwei Chen. Changes of lncRNA expression and its correlation with CD8⁺ T cells in patients with systemic lupus erythematosus [J]. Chinese Journal of Diagnostics(Electronic Edition), 2023, 11(03): 184-189.

Please choose a citation manager

Content to export