二肽基肽酶Ⅳ抑制剂对T细胞迁移的影响

陈运凡; 沈俊杰; 钱程

doi:10.16016/j.1000-5404.201802025

您当前的位置：

首页 >

文章列表页 >

二肽基肽酶Ⅳ抑制剂对T细胞迁移的影响

基础医学 | 更新时间：2026-01-09

- 二肽基肽酶Ⅳ抑制剂对T细胞迁移的影响
- Effect of dipeptidyl peptidase Ⅳ inhibitor on human T cell migration in vitro
- 第三军医大学学报 2018年40卷第16期页码：1450-1455
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家重点研发计划(2016YFC1303405);陆军军医大学(第三军医大学)第一附属医院生物强院科技创新计划(SWH2016LCYB-06)
- DOI：10.16016/j.1000-5404.201802025
  中图分类号：
- 收稿：2018-02-04，
  
  纸质出版：2018-08-30
- 稿件说明：
移动端阅览
陈运凡, 沈俊杰, 钱程. 二肽基肽酶Ⅳ抑制剂对T细胞迁移的影响[J]. 第三军医大学学报, 2018,40(16):1450-1455.

Yunfan CHEN, Junjie SHEN, Cheng QIAN. Effect of dipeptidyl peptidase Ⅳ inhibitor on human T cell migration in vitro[J]. Journal of Third Military Medical University, 2018, 40(16): 1450-1455.
陈运凡, 沈俊杰, 钱程. 二肽基肽酶Ⅳ抑制剂对T细胞迁移的影响[J]. 第三军医大学学报, 2018,40(16):1450-1455. DOI： 10.16016/j.1000-5404.201802025.

Yunfan CHEN, Junjie SHEN, Cheng QIAN. Effect of dipeptidyl peptidase Ⅳ inhibitor on human T cell migration in vitro[J]. Journal of Third Military Medical University, 2018, 40(16): 1450-1455. DOI： 10.16016/j.1000-5404.201802025.

摘要

Abstract

Objective

To explore the effect of dipeptidyl peptidase Ⅳ (DPP Ⅳ) inhibitor on human T cell migration

in vitro

Methods

Flow cytometry was used to detect the expression of CXCR3 in human peripheral T cells from healthy donors.The expression of DPP Ⅳ and CXCL10 in colon cancer LoVo cell line was detected with ELISA.Molecular cloning technique were used to construct LoVo cell lines expressing full-length and DPP Ⅳ-truncated CXCL10 [termed LoVo-CXCL10(1-77) and LoVo-CXCL10(3-77)

respectively].The migration of T cells in response to LoVo cells expressing different forms of CXCL10 and the effect of DPP Ⅳ inhibitor on T cell migration were tested with Transwell assay.

Results

CXCR3 was expressed up to 95% on the surface of activated T cells.LoVo cells expressed DPP Ⅳ at a level as high as 1 956.5±95.6 pg/mL but had a low expression level of CXCL10 of 15.5±0.8 pg/mL.The number of migrating T cells in response to LoVo-CXCL10(1-77) cells reached (9.5±0.9)×10

significantly higher than the number of T cells attracted by LoVo-CXCL10(3-77) cells.DPP Ⅳ inhibitor significantly increased the migration of T cells in response to LoVo-CXCL10(1-77) to the level of (12.3±0.9)×10

Conclusion

DPP Ⅳ inhibits the chemotaxis of T cells to CXCL10

in vitro

and DPP Ⅳ inhibitor can enhance the migration of T cells toward tumor cells.

关键词

Keywords

references

BREMNES R M AL-SHIBLI K DONNEM T The role of tumor-infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis:emphasis on non-small cell lung cancer J Thorac Oncol 2011 6 4 824 833 10.1097/JTO.0b013e3182037b76 BREMNES R M, AL-SHIBLI K, DONNEM T, et al .The role of tumor- infiltrating immune cells and chronic inflammation at the tumor site on cancer development, progression, and prognosis:emphasis on non-small cell lung cancer[J ] .J Thorac Oncol, 2011, 6(4):824-833.DOI:10.1097/JTO.0b013e3182037b76.

NUNES C WONG R MASON M Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression Clin Cancer Res 2012 18 3 678 687 10.1158/1078-0432.CCR-11-2630 NUNES C, WONG R, MASON M, et al .Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression[J ] .Clin Cancer Res, 2012, 18(3):678-687.DOI:10.1158/1078- 0432.CCR-11-2630.

PAGÈS F GALON J DIEU-NOSJEAN M C Immune infiltration in human tumors:a prognostic factor that should not be ignored Oncogene 2010 29 8 1093 1102 10.1038/onc.2009.416 PAGÈS F, GALON J, DIEU-NOSJEAN M C, et al .Immune infiltration in human tumors:a prognostic factor that should not be ignored[J ] .Oncogene, 2010, 29(8):1093-1102.DOI:10.1038/onc.2009.416.

GALON J COSTES A SANCHEZ-CABO F Type, density, and location of immune cells within human colorectal tumors predict clinical outcome Science 2006 313 5795 1960 1964 10.1126/science.1129139 GALON J, COSTES A, SANCHEZ-CABO F, et al .Type, density, and location of immune cells within human colorectal tumors predict clinical outcome[J ] .Science, 2006, 313(5795):1960-1964.DOI:10.1126/science.1129139.

HARLIN H MENG Y PETERSON A C Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment Cancer Res 2009 69 7 3077 3085 10.1158/0008-5472.CAN-08-2281 HARLIN H, MENG Y, PETERSON A C, et al .Chemokine expression in melanoma met astases associated with CD8+ T-cell recruitment[J ] .Cancer Res, 2009, 69(7):3077-3085.DOI:10.1158/0008-5472.CAN-08-2281.

MLECNIK B TOSOLINI M CHAROENTONG P Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer Gastroenterology 2010 138 4 1429 1440 10.1053/j.gastro.2009.10.057 MLECNIK B, TOSOLINI M, CHAROENTONG P, et al .Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer[J ] .Gastroenterology, 2010, 138(4):1429-1440.DOI:10.1053/j.gastro.2009.10.057.

MIKUCKI M E FISHER D T MATSUZAKI J Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints Nat Commun 2015 6 7458 10.1038/ncomms8458 MIKUCKI M E, FISHER D T, MATSUZAKI J, et al .Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell traffickin g across tumour vascular checkpoints[J ] .Nat Commun, 2015, 6:7458.DOI:10.1038/ ncomms8458.

YU D M YAO T W CHOWDHURY S The dipeptidyl peptidase Ⅳ family in cancer and cell biology FEBS J 2010 277 5 1126 1144 10.1111/j.1742-4658.2009.07526.x YU D M, YAO T W, CHOWDHURY S, et al .The dipeptidyl peptidase Ⅳ family in cancer and cell biology[J ] .FEBS J, 2010, 277(5):1126-1144.DOI:10.1111/j.1742-4658.2009.07526.x.

BECKENKAMP A DAVIES S WILLIG J B DPPIV/CD26:a tumor suppressor or a marker of malignancy Tumour Biol 2016 37 6 7059 7073 10.1007/s13277-016-5005-2 BECKENKAMP A, DAVIES S, WILLIG J B, et al .DPPIV/CD26:a tumor suppressor or a marker of malignancy[J ] .Tumour Biol, 2016, 37(6):7059-7073.DOI:10.1007/s13277-016-5005-2.

OHNUMA K TAKAHASHI N YAMOCHI T Role of CD26/dipeptidyl peptidase Ⅳ in human T cell activation and function Front Biosci 2008 13 2299 2310 10.2741/2844 OHNUMA K, TAKAHASHI N, YAMOCHI T, et al .Role of CD26/dipeptidyl peptidase Ⅳ in human T cell activation and function[J ] .Front Biosci, 2008, 13:2299-2310.DOI:10.2741/2844.

DEACON C F Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes:a comparative review Diabetes Obes Metab 2011 13 1 7 18 10.1111/j.1463-1326.2010.01306.x DEACON C F.Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes:a comparative review[J].Diabetes Obes Metab, 2011, 13(1):7-18.DOI:10.1111/j.1463-1326.2010.01306.x.

MILLER S ST ONGE E L Sitagliptin:a dipeptidyl peptidase Ⅳ inhibitor for the treatment of type 2 diabetes Ann Pharmacother 2006 40 7-8 1336 1343 10.1345/aph.1G665 MILLER S, ST ONGE E L.Sitagliptin:a dipeptidyl peptidase Ⅳ inhibitor for the treatment of type 2 diabetes[J].Ann Pharmacother, 2006, 40(7-8):1336-1343.DOI:10.1345/aph.1G665.

MULVIHILL E E DRUCKER D J Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors Endocr Rev 2014 35 6 992 1019 10.1210/er.2014-1035 MULVIHILL E E, DRUCKER D J.Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors[J].Endocr Rev, 2014, 35(6):992-1019.DOI:10.1210/er.2014-1035.

DE CHIARA L RODRÍGUEZ-PIÑEIRO A M RODRÍGUEZ-BERROCAL F J Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas BMC Cancer 2010 10 333 10.1186/1471-2407-10-333 DE CHIARA L, RODRÍGUEZ-PIÑEIRO A M, RODRÍGUEZ- BERROCAL F J, et al .Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas[J ] .BMC Cancer, 2010, 10:333.DOI:10.1186/1471-2407-10-333.

LAM C S CHEUNG A H WONG S K Prognostic significance of CD26 in patients with colorectal cancer PLoS ONE 2014 9 5 e98582 10.1371/journal.pone.0098582 LAM C S, CHEUNG A H, WONG S K, et al .Prognostic significance of CD26 in patients with colorectal cancer[J ] .PLoS ONE, 2014, 9(5):e98582.DOI:10.1371/journal.pone.0098582.

YANG Y Cancer immunotherapy:harnessing the immune system to battle cancer J Clin Invest 2015 125 9 3335 3337 10.1172/JCI83871 YANG Y.Cancer immunotherapy:harnessing the immune system to battle cancer[J].J Clin Invest, 2015, 125(9):3335-3337.DOI:10.1172/ JCI83871.

CHOW M T LUSTER A D Chemokines in cancer Cancer Immunol Res 2014 2 12 1125 1131 10.1158/2326-6066.CIR-14-0160 CHOW M T, LUSTER A D.Chemokines in cancer[J].Cancer Immunol Res, 2014, 2(12):1125-1131.DOI:10.1158/2326-6066.CIR-14- 0160.

FRANCISZKIEWICZ K BOISSONNAS A BOUTET M Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response Cancer Res 2012 72 24 6325 6332 10.1158/0008-5472.CAN-12-2027 FRANCISZKIEWICZ K, BOISSONNAS A, BOUTET M, et al .Role of chemokines and chemokine receptors in shaping the effector phase of the antitumor immune response[J ] .Cancer Res, 2012, 72(24):6325-6332.DOI:10.1158/0008-5472.CAN-12-2027.

NASSER M W ELBAZ M AHIRWAR D K Conditioning solid tumor microenvironment through inflammatory chemokines and S100 family proteins Cancer Lett 2015 365 1 11 22 10.1016/j.canlet.2015.05.002 NASSER M W, ELBAZ M, AHIRWAR D K, et al .Conditioning solid tumor microenvironment through inflammatory chemokines and S100 family proteins[J ] .Cancer Lett, 2015, 365(1):11-22.DOI:10.1016/j.canlet.2015.05.002.

SARVAIYA P J GUO D ULASOV I Chemokines in tumor progression and metastasis Oncotarget 2013 4 12 2171 2185 10.18632/oncotarget.1426 SARVAIYA P J, GUO D, ULASOV I, et al .Chemokines in tumor progression and metastasis[J ] .Oncotarget, 2013, 4(12):2171-2185.DOI:10.18632/oncotarget.1426.

CASROUGE A BISIAUX A STEPHEN L Discrimination of agonist and antagonist forms of CXCL10 in biological samples Clin Exp Immunol 2012 167 1 137 148 10.1111/j.1365-2249.2011.04488.x CASROUGE A, BISIAUX A, STEPHEN L, et al .Discrimination of agonist and antagonist forms of CXCL10 in biological samples[J ] .Clin Exp Immunol, 2012, 167(1):137-148.DOI:10.1111/ j.1365-2249.2011.04488.x.

MORTIER A GOUWY M VAN DAMME J Effect of posttranslational processing on the in vitro and in vivo activity of chemokines Exp Cell Res 2011 317 5 642 654 10.1016/j.yexcr.2010.11.016 MORTIER A, GOUWY M, VAN DAMME J, et al .Effect of posttranslational processing on the in vitro and in vivo activity of chemokines[J ] .Exp Cell Res, 2011, 317(5):642-654.DOI:10.1016/ j.yexcr.2010.11.016.

KARAGIANNIS T BOURA P TSAPAS A Safety of dipeptidyl peptidase 4 inhibitors:a perspective review Ther Adv Drug Saf 2014 5 3 138 146 10.1177/2042098614523031 KARAGIANNIS T, BOURA P, TSAPAS A.Safety of dipeptidyl peptidase 4 inhibitors:a perspective review[J].Ther Adv Drug Saf, 2014, 5(3):138-146.DOI:10.1177/2042098614523031.

ANZ D KRUGER S HAUBNER S The dipeptidylpeptidase-Ⅳ inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses Diabetes Obes Metab 2014 16 6 569 572 10.1111/dom.12246 ANZ D, KRUGER S, HAUBNER S, et al .The dipeptidylpeptidase-Ⅳ inhibitors sitagliptin, vildagliptin and saxagliptin do not impair innate and adaptive immune responses[J ] .Diabetes Obes Metab, 2014, 16(6):569-572.DOI:10.1111/dom.12246.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

增生性瘢痕与瘢痕疙瘩上皮间质转化及CD26表达的异质性研究

Stathmin通过促进伪足形成介导TNF-α诱导的皮肤成纤维细胞迁移

骨髓间充质干细胞外泌体调控肾癌细胞胆固醇代谢及其增殖、侵袭和迁移

UHRF2通过PI3K/Akt信号通路促进肝细胞癌细胞的增殖和转移

胎盘间充质干细胞外泌体对高糖培养的成纤维细胞衰老的影响