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IL-1? (Interleukin-1?) and TNF-? (Tumor Necrosis Factor-?) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

ABSTRACT: OBJECTIVE:Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1? versus TNF-? (tumor necrosis factor-?) in abdominal aortic aneurysm formation. APPROACH AND RESULTS:IL-1? was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1? and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1? deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-?. Bone marrow-derived macrophages from IL-1?-/- and TNF-?-/- mice were polarized to an M1 phenotype. TNF-? deletion, but not IL-1? deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-?-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1?-/- macrophages. CONCLUSIONS:Although IL-1? is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-?. The differential effects of IL-1? and TNF-? inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1? and TNF-? antibody therapies in management of inflammatory diseases.

SUBMITTER: Batra R

PROVIDER: S-EPMC7450719 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

Batra Rishi R Suh Melissa K MK Carson Jeffrey S JS Dale Matthew A MA Meisinger Trevor M TM Fitzgerald Matthew M Opperman Patrick J PJ Luo Jiangtao J Pipinos Iraklis I II Xiong Wanfen W Baxter B Timothy BT

Arteriosclerosis, thrombosis, and vascular biology 20171207 2

<h4>Objective</h4>Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) i ...[more]

PMID: 29217508

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Project description:The role of resolvins in abdominal aortic aneurysm (AAA) has not been established. We hypothesized that treatment with D-series resolvins (RvD2 or RvD1) would attenuate murine AAA formation through alterations in macrophage polarization and cytokine expression. Male C57/B6 mice (n = 9 per group) 8 to 12 wk old received RvD2 (100 ng/kg/treatment), RvD1 (100 ng/kg/treatment), or vehicle only every third day beginning 3 d before abdominal aortic perfusion with elastase as prevention. Aortas were collected 14 d after elastase perfusion. Cytokine analysis (n = 5 per group) or confocal microscopy (n = 4 per group) was performed. In a separate experiment, RvD2 was provided to mice with small AAAs 3 d after elastase treatment (n = 8 per group). Additionally, apolipoprotein E knockout mice treated with angiotensin II (1000 ng/kg) were treated with RvD2 or vehicle alone (n = 10 per group) in a nonsurgical model of AAA. To determine the effect of RvD2 on macrophage polarization, confocal staining for macrophages, M1 and M2 macrophage subtypes, ?-actin, and DAPI was performed. Mean aortic dilation was 96 ± 13% for vehicle-treated mice, 57 ± 9.7% for RvD2-treated mice, and 61 ± 11% for RvD1-treated mice (P < 0.0001). Proinflammatory cytokines macrophage chemotactic protein 1, C-X-C motif ligand 1, and IL-1? were significantly elevated in control animals compared to RvD2- and RvD1-treated animals (P < 0.05), resulting in a reduction of matrix metalloproteinase 2 and 9 activity in resolvin-treated mice in both elastase and angiotensin II models. Treatment of existing small AAAs with RvD2 demonstrated a 25% reduction in aneurysm size at d 14 compared to vehicle alone (P = 0.018). Confocal histology demonstrated a prevalence of M2 macrophages within the aortic medium in mice treated with RvD2. Resolvin D2 exhibits a potent protective effect against experimental AAA formation. Treatment with RvD2 significantly influences macrophage polarization and decreases several important proinflammatory cytokines. Resolvins and the alteration of macrophage polarization represent potential future targets for prevention of AAA.-Pope, N. H., Salmon, M., Davis, J. P., Chatterjee, A., Su, G., Conte, M. S., Ailawadi, G., Upchurch, G. R., Jr. D-series resolvins inhibit murine abdominal aortic aneurysm formation and increase M2 macrophage polarization.

Dataset Information

IL-1? (Interleukin-1?) and TNF-? (Tumor Necrosis Factor-?) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

Publications

IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization.

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