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Interleukin 6 may be related to indoleamine 2,3-dioxygense function in M2 macrophages treated with small dense LDL
Parisa Hassanpour1, Abdollah Amirfarhangi2, Syed Reza Hosseini-Fard3
1Iran University of Medical Sciences, School of Medicine, International Branch, Tehran, Iran.
Abstract:
Macrophages are known as important immune cells involved in the improvement of atherosclerosis plaques. The M2 macrophages are beneficial because scavenging the non-functional components in vessel sub-endothelial space. In this study, we investigated the effects of small dense LDL (sdLDL) on the changes of indoleamine 2,3-dioxygense (IDO) and interleukin (IL6) in the differentiated M2 macrophages. The patients were selected from who underwent coronary artery angiography. The monocytes were isolated from the whole blood samples of healthy (<5% stenosis) and patient (>70% stenosis; SVD, 2VD and 3VD) subjects and, were differentiated into M2 macrophages. The IDO gene expression, activity and IL6 values were measured by RT-qPCR, colorimetry and ELISA techniques, respectively. In contrast with healthy group, the IDO gene expression and activity were significantly reduced in SVD and 2VD groups (P<0.05). Furthermore, they were conversely associated to secretion of IL6. In conclusion, the data suggested that inflammatory responses in M2 macrophages differentiated from monocytes of patients after treatment of sdLDL may be related to the reduced IDO function.
Insights
Small dense LDL (sdLDL) reduces indoleamine 2,3-dioxygenase (IDO) function in M2 macrophages from atherosclerosis patients. This reduction is linked to increased interleukin-6 (IL6) secretion, suggesting a role in inflammatory responses.
Area of Science:
- Immunology
- Cardiovascular Research
- Molecular Biology
Background:
- Macrophages, particularly M2 macrophages, play a crucial role in resolving atherosclerosis by clearing debris from blood vessels.
- Small dense LDL (sdLDL) is implicated in cardiovascular disease progression.
- The interplay between sdLDL, indoleamine 2,3-dioxygenase (IDO), and interleukin-6 (IL6) in M2 macrophages is not fully understood.
Purpose of the Study:
- To investigate the impact of sdLDL on IDO and IL6 in M2 macrophages.
- To compare these effects in M2 macrophages derived from healthy individuals versus patients with varying degrees of coronary artery stenosis.
Main Methods:
- Monocytes were isolated from healthy subjects and patients undergoing coronary angiography (SVD, 2VD, 3VD).
- Monocytes were differentiated into M2 macrophages.
- IDO gene expression (RT-qPCR), IDO activity (colorimetry), and IL6 levels (ELISA) were measured.
Main Results:
- IDO gene expression and activity were significantly reduced in M2 macrophages from patients with single- (SVD) and two-vessel disease (2VD) compared to healthy controls.
- Reduced IDO function showed an inverse correlation with IL6 secretion.
- These changes were observed following exposure to sdLDL.
Conclusions:
- sdLDL may impair the beneficial functions of M2 macrophages in atherosclerosis.
- The observed reduction in IDO function and concomitant increase in IL6 suggest a pro-inflammatory shift in M2 macrophages.
- These findings highlight a potential mechanism linking sdLDL to exacerbated inflammatory responses in atherosclerosis.
