Dataset Information

Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

ABSTRACT:

Objectives

Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).

Methods and results

We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured temporal changes of MIF in plasma. Expression of MIF, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR. Compared to controls, plasma levels of MIF and IL-6 were significantly elevated at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by PBMCs from MI patients was unchanged at admission, but significantly increased at 72 h. Addition of MIF activated cultured PBMCs by upregulating expression of inflammatory molecules and also synergistically enhanced stimulatory action of IL-1? which were inhibited by anti-MIF interventions. In a mouse MI model we observed similar changes in circulating MIF as seen in patients, with reciprocal significant increases in plasma MIF and reduction of MIF content in the infarct myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at 72 h post-MI and was associated with robust macrophage infiltration. Further, anti-MIF intervention significantly reduced inflammatory cell infiltration and expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac rupture in mice post-MI.

Conclusion

MI leads to a rapid release of MIF from the myocardium into circulation. Subsequently MIF facilitates PBMC production of pro-inflammatory mediators and myocardial inflammatory infiltration. Attenuation of these events, and post-MI cardiac rupture, by anti-MIF interventions suggests that MIF could be a potential therapeutic target following MI.

SUBMITTER: White DA

PROVIDER: S-EPMC3788072 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

White David A DA Fang Lu L Chan William W Morand Eric F EF Kiriazis Helen H Duffy Stephen J SJ Taylor Andrew J AJ Dart Anthony M AM Du Xiao-Jun XJ Gao Xiao-Ming XM

PloS one 20131001 10

<h4>Objectives</h4>Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, has been implicated in the pathogenesis of multiple inflammatory disorders. We determined changes in circulating MIF levels, explored the cellular source of MIF, and studied the role of MIF in mediating inflammatory responses following acute myocardial infarction (MI).<h4>Methods and results</h4>We recruited 15 patients with MI, 10 patients with stable angina and 10 healthy volunteers and measured tempo ...[more]

PMID: 24098445

Similar Datasets

Project description:BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

Project description:Background: Acute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive. Methods: Ten AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells. Results: We identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory_x0002_related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell?cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture. Conclusions: Our studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

Project description:Hirschsprung disease (HSCR) is a rare congenital anomaly characterized by the absence of enteric ganglia in the distal intestinal tract. While classified as a multigenic disorder, the altered function of the RET tyrosine kinase receptor is responsible for the majority of the pathogenesis of HSCR. Recent evidence demonstrate a strong association between RET and the homeostasis of immune system. Here, we utilize a unique cohort of fifty HSCR patients to fully characterize the expression of RET receptor on both innate (monocytes and Natural Killer lymphocytes) and adaptive (B and T lymphocytes) human peripheral blood mononuclear cells (PBMCs) and to explore the role of RET signaling in the immune system. We show that the increased expression of RET receptor on immune cell subsets from HSCR individuals correlates with the presence of loss-of-function RET mutations. Moreover, we demonstrate that the engagement of RET on PBMCs induces the modulation of several inflammatory genes. In particular, RET stimulation with glial-cell line derived neurotrophic factor family (GDNF) and glycosyl-phosphatidylinositol membrane anchored co-receptor ?1 (GFR?1) trigger the up-modulation of genes encoding either for chemokines (CCL20, CCL2, CCL3, CCL4, CCL7, CXCL1) and cytokines (IL-1?, IL-6 and IL-8) and the down-regulation of chemokine/cytokine receptors (CCR2 and IL8-R?). Although at different levels, the modulation of these "RET-dependent genes" occurs in both healthy donors and HSCR patients. We also describe another set of genes that, independently from RET stimulation, are differently regulated in healthy donors versus HSCR patients. Among these "RET-independent genes", there are CSF-1R, IL1-R1, IL1-R2 and TGF?-1, whose levels of transcripts were lower in HSCR patients compared to healthy donors, thus suggesting aberrancies of inflammatory responses at mucosal level. Overall our results demonstrate that immune system actively participates in the physiopathology of HSCR disease by modulating inflammatory programs that are either dependent or independent from RET signaling.

Project description:Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic diseases. The incidence of AMI in some countries increases year by year, and shows younger trend. Some study indicated that abnormal expression of lncRNAs was closely related to cardiovascular disease. The aim of this study was to examine the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with AMI through controlled studies.In the present study, we examined the lncRNA and mRNA expression profiles in 8 patients with AMI, with 7 NCA (noncoronary artery) subjects as controls using RNA sequencing protocol (RNA-seq) on the Illumina HiSeq 4000 platform. The differentially expressed lncRNAs were selected for bioinformatic analysis including gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Quantitative real time PCR (qRT-PCR) was used to confirm the differential expression of lncRNAs.We kept about 11.29 gigabase (Gb) high-quality sequence data while the Q30 ranged from 94.39% to 95.19% for each sample. Compared to the lncRNA expression profiles of NCA controls, a total of 106 differentially expressed lncRNAs were discriminated in AMI patients, including 40 upregulated lncRNAs and 66 downregulated lncRNAs (P?<?.05). Among the genes corresponding to the identified mRNAs, 2905 genes are involved in biological processes, 339 in cellular components, and 501 in molecular functions. Based on the KEGG pathway analysis, the most enriched pathways corresponding to the differentially expressed lncRNAs were associated with systemic lupus erythematosus, alcoholism, oxidative phosphorylation, Parkinson's disease and viral carcinogenesis, and so on. Further, 3 upregulated and 3 downregulated lncRNAs were randomly selected for qRT-PCR verification and the results of qRT-PCR were consistent with the findings obtained from RNA sequencing analysis.As a result, differential expression profiles of lncRNAs in AMI were identified in our study. The results suggested that lncRNAs may play important roles in the biological and pathological processes of AMI. These findings may provide useful reference for the early diagnosis and risk stratification of AMI patients. To enlarge the sample size in the next step will be needed for further research to confirm our results.

Dataset Information

Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

Objectives

Methods and results

Conclusion

Publications

Pro-inflammatory action of MIF in acute myocardial infarction via activation of peripheral blood mononuclear cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets