Related Experiment Video
Updated: Dec 30, 2025
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Inhibition of inflammation-mediated DPP-4 expression by linagliptin increases M2 macrophages in atherosclerotic
Shuhei Nishida1, Takeshi Matsumura1, Takafumi Senokuchi1
1Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Background And Aims:
Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to suppress atherosclerosis progression in atherosclerotic mouse models through unclear mechanisms. In this study, we investigated the effect of the DPP-4 inhibitor, linagliptin, on macrophage polarization in vitro and in vivo.
Methods:
Mouse bone marrow macrophages (BMMs) were used in in vitro assays. High fat diet (HFD)-fed Apoe-/- mice were treated orally with linagliptin (10 mg/kg-1•day-1) or a vehicle (water) control.
Results:
In in vitro assays using BMMs, treatment with LPS and IFNγ decreased the mRNA-expression levels of alternatively activated macrophage (M2) markers, and linagliptin treatment prevented these reductions. The mRNA levels of M2 markers and the number of M2 macrophages in the aorta were higher in linagliptin groups than in control groups. Linagliptin decreased the size of atherosclerotic lesions in HFD-fed Apoe-/- mice. Interestingly, inflammatory stimulation increased DPP-4 expression, and linagliptin suppressed these effects in BMMs. Treatment with DPP-4 small-interfering RNA (siRNA) reproduced linagliptin-mediated alteration of M2 polarization.
Conclusions:
Linagliptin increased M2 macrophage polarization by inhibiting DPP-4 expression and activity. These findings may indicate the beneficial effects of DPP-4 inhibitors on the progression of diabetic macrovascular complications.
Insights
Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, promotes M2 macrophage polarization by inhibiting DPP-4. This suggests DPP-4 inhibitors may benefit diabetic macrovascular complications.
Area of Science:
- Immunology
- Cardiovascular Research
- Pharmacology
Background:
- Dipeptidyl peptidase-4 (DPP-4) inhibitors are known to potentially suppress atherosclerosis, but the mechanisms remain unclear.
- Macrophage polarization plays a critical role in the development and progression of atherosclerosis.
Purpose of the Study:
- To investigate the effect of the DPP-4 inhibitor linagliptin on macrophage polarization in vitro and in vivo.
- To elucidate the role of DPP-4 in regulating macrophage phenotype during atherosclerosis.
Main Methods:
- In vitro studies utilized mouse bone marrow macrophages (BMMs) stimulated with LPS and IFNγ.
- In vivo studies involved high-fat diet-fed Apoe-/- mice treated with linagliptin or vehicle control.
- DPP-4 expression and activity were assessed, along with M2 macrophage markers and atherosclerotic lesion size.
Main Results:
- Linagliptin treatment prevented the decrease in M2 macrophage markers induced by inflammatory stimuli in vitro.
- In vivo, linagliptin increased M2 macrophage markers and reduced atherosclerotic lesion size in Apoe-/- mice.
- Inflammatory stimulation increased DPP-4 expression, which was suppressed by linagliptin; DPP-4 siRNA mimicked linagliptin's effects on M2 polarization.
Conclusions:
- Linagliptin enhances M2 macrophage polarization by inhibiting DPP-4 expression and activity.
- These findings suggest a potential therapeutic benefit of DPP-4 inhibitors in mitigating diabetic macrovascular complications.
More Related Videos
Related Concept Videos
01:23Dipeptidyl Peptidase 4 Inhibitors
01:38Inflammation
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:19Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
01:26Atherosclerosis III: Management