ABSTRACT
Interleukin- (IL-) 17 is increased in acute myocardial infarction (AMI) and plays a key role in inflammatory diseases through its involvement in the activation of leukocytes. Here, we describe for the first time the effect of IL-17 in the migration and activation of monocyte subsets in patients during ST-segment elevation myocardial infarction (STEMI) and post-STEMI. We analyzed the circulating levels of IL-17 in patient plasma. A gradual increase in IL-17 was found in STEMI and post-STEMI patients. Additionally, IL-17 had a powerful effect on the recruitment of CD14++CD16+/CD14+CD16++ monocytes derived from patients post-STEMI compared with the monocytes from patients with STEMI, suggesting that IL-17 recruits monocytes with inflammatory activity post-STEMI. Furthermore, IL-17 increased the expression of TLR4 on CD14 + CD16 - and CD14++CD16+/CD14+CD16++ monocytes post-STEMI and might enhance the response to danger-associated molecular patterns post-STEMI. Moreover, IL-17 induced secretion of IL-6 from CD14++CD16- and CD14++CD16+/CD14+CD16++ monocytes both in STEMI and in post-STEMI, which indicates that IL-17 has an effect on the secretion of proinflammatory cytokines from monocytes during STEMI and post-STEMI. Overall, we demonstrate that in STEMI and post-STEMI, IL-17 is increased and induces the migration and activation of monocyte subsets, possibly contributing to the inflammatory response through TLR4 and IL-6 secretion.
Subject(s)
Endothelium, Vascular/metabolism , Interleukin-17/metabolism , Monocytes/immunology , Myocardial Infarction/immunology , Adult , Aged , Aged, 80 and over , Electrocardiography , Endothelium, Vascular/pathology , Female , Human Umbilical Vein Endothelial Cells , Humans , Interleukin-6/metabolism , Lipopolysaccharide Receptors/metabolism , Male , Middle Aged , Receptors, IgG/metabolism , Toll-Like Receptor 4/metabolismABSTRACT
Acute myocardial infarction (AMI) is a leading cause of death worldwide. Myocardial necrosis generates damage signals and triggers an intense inflammatory response. Many cytokines that contribute to repair tissue can also cause adverse left ventricular remodeling and heart failure. Several studies have revealed that interleukin-17 (IL-17) is a cytokine with a potential role in AMI. IL-17 plays an important role in the immune response and affects the production of different inflammatory mediators in several types of cells, involved in the damage or scar process in myocardial tissue. In this review, we will discuss the current knowledge of the role of IL-17 in AMI and the effect of IL-17 in different cells, such as cardiomyocytes, smooth muscle cells and immune system cells, in AMI pathogenesis.
Subject(s)
Interleukin-17/metabolism , Myocardial Infarction/metabolism , Animals , Humans , Inflammation/pathology , Models, Biological , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Receptors, Interleukin-17/metabolismABSTRACT
BACKGROUND: Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). METHODS: Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. RESULTS: The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. CONCLUSION: Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.
