DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions
Valeria De Nigris,1 Francesco Prattichizzo,2 Hiroaki Iijima,3 Antonio Ceriello2 1Institut d’Investigación Biomédiques August Pi i Sunyer, Barcelona, Spain; 2IRCCS MultiMedica, Milan, Italy; 3Medical Affairs Department, Ikuyaku. Integrated Value Development Division, M...
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Dove Medical Press
2021
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oai:doaj.org-article:f5ae36c0074d4d2592b19f4b27d51f572021-12-02T18:18:27ZDPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions1178-7007https://doaj.org/article/f5ae36c0074d4d2592b19f4b27d51f572021-04-01T00:00:00Zhttps://www.dovepress.com/dpp-4-inhibitors-have-different-effects-on-endothelial-low-grade-infla-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Valeria De Nigris,1 Francesco Prattichizzo,2 Hiroaki Iijima,3 Antonio Ceriello2 1Institut d’Investigación Biomédiques August Pi i Sunyer, Barcelona, Spain; 2IRCCS MultiMedica, Milan, Italy; 3Medical Affairs Department, Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, JapanCorrespondence: Valeria De NigrisInsititut d’Investigacions Biomèdiques August Pi i Sunyer, C/Rosselló, 149-153, Barcelona, 08036, SpainTel +34932275400 Ext. 4562Fax +34932279240Email valeriadenigris@yahoo.itPurpose: We explored the anti-inflammatory role of the DPP-4 inhibitor teneligliptin, using sitagliptin as comparator, in different in vitro models of low-grade inflammation (LGI), evaluating the hyperglycemia-induced endothelial inflammation, the macrophage polarization, and the endothelium–macrophage interaction.Methods: The effects of DPP-4 and its inhibitors on macrophage polarization were evaluated in THP-1 cells by measuring mRNA expression of M1-M2 markers. HUVEC cells were used to analyze the effects of DPP-4 inhibitors on endothelial inflammation under normal and high glucose conditions. To evaluate the link between eNO and M1-M2 polarization, HUVECs were transfected with eNOS siRNA and co-cultured with THP-1 cells. The effects of DPP-4 inhibitors on macrophage polarization and eNO content were evaluated in a co-culture model of differentiated THP-1 cells + HUVECs under normal glucose (NG), high glucose (HG) and high metabolic memory (HM) conditions.Results: DPP-4 regulated M1/M2 macrophage polarization. Teneligliptin reduced M1 and enhanced M2 macrophage phenotype under DPP-4 stimulation, and attenuated hyperglycemia-induced endothelial inflammation. In THP-1 cells co-cultured with eNOS depleted HUVECs, M1 markers were enhanced, while M2 reduced, indicating an important role of eNO in polarization to M2 phenotype. In the co-culture model with HUVECs exposed to HG and HM, teneligliptin reduced M1 and enhanced M2 population, by increasing eNO levels. The anti-inflammatory effects of sitagliptin were not observed in these LGI models.Conclusion: Teneligliptin, but not sitagliptin, has anti-inflammatory effects in the various LGI models, by promoting a switch from M1 toward M2 phenotype and by decreasing hyperglycaemia-induced endothelial inflammation, suggesting that effects for LGI are different among DPP-4 inhibitors.Keywords: DPP-4 inhibitors, low-grade inflammation, teneligliptin, macrophage polarization, endothelial inflammation, endothelial NO, high glucose, antioxidant defenseDe Nigris VPrattichizzo FIijima HCeriello ADove Medical Pressarticledpp-4 inhibitorslow grade inflammationteneligliptinmacrophage polarizationendothelial inflammationendothelial nohigh glucoseantioxidant defenseSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1519-1531 (2021) |
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dpp-4 inhibitors low grade inflammation teneligliptin macrophage polarization endothelial inflammation endothelial no high glucose antioxidant defense Specialties of internal medicine RC581-951 |
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dpp-4 inhibitors low grade inflammation teneligliptin macrophage polarization endothelial inflammation endothelial no high glucose antioxidant defense Specialties of internal medicine RC581-951 De Nigris V Prattichizzo F Iijima H Ceriello A DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| description |
Valeria De Nigris,1 Francesco Prattichizzo,2 Hiroaki Iijima,3 Antonio Ceriello2 1Institut d’Investigación Biomédiques August Pi i Sunyer, Barcelona, Spain; 2IRCCS MultiMedica, Milan, Italy; 3Medical Affairs Department, Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, JapanCorrespondence: Valeria De NigrisInsititut d’Investigacions Biomèdiques August Pi i Sunyer, C/Rosselló, 149-153, Barcelona, 08036, SpainTel +34932275400 Ext. 4562Fax +34932279240Email valeriadenigris@yahoo.itPurpose: We explored the anti-inflammatory role of the DPP-4 inhibitor teneligliptin, using sitagliptin as comparator, in different in vitro models of low-grade inflammation (LGI), evaluating the hyperglycemia-induced endothelial inflammation, the macrophage polarization, and the endothelium–macrophage interaction.Methods: The effects of DPP-4 and its inhibitors on macrophage polarization were evaluated in THP-1 cells by measuring mRNA expression of M1-M2 markers. HUVEC cells were used to analyze the effects of DPP-4 inhibitors on endothelial inflammation under normal and high glucose conditions. To evaluate the link between eNO and M1-M2 polarization, HUVECs were transfected with eNOS siRNA and co-cultured with THP-1 cells. The effects of DPP-4 inhibitors on macrophage polarization and eNO content were evaluated in a co-culture model of differentiated THP-1 cells + HUVECs under normal glucose (NG), high glucose (HG) and high metabolic memory (HM) conditions.Results: DPP-4 regulated M1/M2 macrophage polarization. Teneligliptin reduced M1 and enhanced M2 macrophage phenotype under DPP-4 stimulation, and attenuated hyperglycemia-induced endothelial inflammation. In THP-1 cells co-cultured with eNOS depleted HUVECs, M1 markers were enhanced, while M2 reduced, indicating an important role of eNO in polarization to M2 phenotype. In the co-culture model with HUVECs exposed to HG and HM, teneligliptin reduced M1 and enhanced M2 population, by increasing eNO levels. The anti-inflammatory effects of sitagliptin were not observed in these LGI models.Conclusion: Teneligliptin, but not sitagliptin, has anti-inflammatory effects in the various LGI models, by promoting a switch from M1 toward M2 phenotype and by decreasing hyperglycaemia-induced endothelial inflammation, suggesting that effects for LGI are different among DPP-4 inhibitors.Keywords: DPP-4 inhibitors, low-grade inflammation, teneligliptin, macrophage polarization, endothelial inflammation, endothelial NO, high glucose, antioxidant defense |
| format |
article |
| author |
De Nigris V Prattichizzo F Iijima H Ceriello A |
| author_facet |
De Nigris V Prattichizzo F Iijima H Ceriello A |
| author_sort |
De Nigris V |
| title |
DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| title_short |
DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| title_full |
DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| title_fullStr |
DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| title_full_unstemmed |
DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions |
| title_sort |
dpp-4 inhibitors have different effects on endothelial low-grade inflammation and on the m1-m2 macrophage polarization under hyperglycemic conditions |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/f5ae36c0074d4d2592b19f4b27d51f57 |
| work_keys_str_mv |
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| _version_ |
1718378309694259200 |