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The Preliminary Study of Interleukin -22 Effect on the Pathogenesis of Atherosclerosis

Author: SunZuo
Tutor: ZhongRenQian
School: Second Military Medical University
Course: Clinical Laboratory Science
Keywords: Interleukin- 22 Atherosclerosis Oxidized low-density lipoprotein Human umbilical vein endothelial cells Apoptosis
CLC: R543.5
Type: Master's thesis
Year: 2011
Downloads: 126
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Abstract

As the global population is increasingly aging, cardiovascular and cerebrovascular diseases have become a class of serious harm to human health, disease, morbidity and mortality rates remain high. And as these serious cardiovascular and cerebrovascular diseases start lesions of atherosclerosis (AS) is a complex multifactorial disease, the pathogenesis is not clear. Study the pathogenesis of AS, for the AS control strategies in the development of great significance. AS pathogenesis lipid infiltration doctrines, doctrines, and damage response doctrine of platelet aggregation and thrombus formation, a number of scholars in recent years on the basis of the doctrine in the damage response of the inflammatory response doctrine that the various risk factors caused by intra-arterial membrane damage is a the AS initiating link, and chronic inflammatory responses throughout the development of AS always. The study found that the endothelial cell barrier as vascular disease risk factors in the blood is in direct contact with ox-LDL (oxidized LDL) is one of the key risk factors that lead to endothelial dysfunction. Damaged endothelial conformational and physiological changes, secretion of chemokines and cytokines, recruitment of mononuclear inflammatory cells such as macrophages gathered amplifies the inflammatory immune response in the damaged blood vessels partial damaged endothelial cell apoptosis necrosis, endothelial barrier destroy the integrity, thus exacerbating atherosclerosis formation. IL-22 is an immune medium Renauld found equal to 2000, which is produced by activated T cells, NK cells and other immune cells, specifically acting on the body cells, especially epithelial cells, without affecting the function of immune cells. A large number of recent studies found to play a protective or pathogenic role of IL-22 in a variety of immune and inflammatory diseases. Findings, IL-22 may enhance keratinocyte proliferation and promote the acute phase response proteins and inflammatory cell chemokine expression resulted in the injury of skin psoriasis; mice arthritis, IL-22 inhibition of collagen and IgG generated to promote tissue inflammation; were involved in IL-22 in influenza infection and Gram-negative bacteria pneumonia mediated host defense function; Sugimoto found in a mouse model of ulcerative colitis, IL-22 is able to improve the intestinal inflammation. However, few studies involving the biological role of IL-22 in the cardiovascular system. Chang et al in 2006 found that non-immune cells of the endothelium, smooth muscle cells, such as cardiovascular, but also the role of IL-22 targets; Gangemi found that IL-22 may be associated with the course of chronic heart failure in 2010. Tip IL-22 may be involved in the chronic inflammatory response of the cardiovascular system. Based on the status of the above studies, we speculated that the IL-22 may be by acting on vascular endothelial cells or smooth muscle cells involved in the risk factor in the blood caused by vascular chronic inflammation, or even formed atherosclerotic process. Then, IL-22 play what role in atherosclerosis it? Whether it can be used as a therapeutic target synergies in the elderly population, a high incidence of diseases, such as heart failure, obstructive pulmonary disease, fatty liver, enteritis role of an aging population gospel? order to confirm the above inference, from the following aspects of research: 1) detection of atherosclerosis in patients in vivo expression of IL-22, analysis of its correlation with disease; 2) Determination IL-22 receptor expression in human vascular endothelial cells; 3) the use of real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) technology, screening IL-22 ox-LDL induced endothelial damage may be involved in the regulation of target molecules; 4) by in vitro experiments verify the effect and mechanism of IL-22 on cell function. The first part of the expression of IL-22 in peripheral blood of patients with atherosclerosis patients by RT-PCR detection of coronary artery disease (CAD) in peripheral blood mononuclear cells (PBMC) expression of IL-22mRNA ELISA detected The serum level of expression, from the analysis of gene and protein levels of IL-22 and atherosclerosis hardening, to provide clues basis for further understanding of the role of IL-22 in atherosclerosis. The results show that the presence of IL-22 mRNA expression As peripheral blood of patients in PBMC. CAD patients according to the severity of coronary lesions grouped after statistical analysis found the vascular stenosis lt; 50% of coronary patients with early lesions IL-22 serum levels significantly higher than coronary stenosis group (P lt; 0.01) and IL-22 expression levels show a downward trend with the increase in coronary stenosis and the number of diseased vessels. The prompt negative correlation between IL-22 and atherosclerosis extent of, and may play a significant role in the process of coronary stenosis early lesions. IL-22 concentration volume showed no correlation with TCHO, TG, LDL-C expression. The second part of IL-22 participate in oxidized LDL-induced atherosclerotic mechanism of the first part of the study showed that IL-22 and atherosclerosis there is a correlation. Whether IL-22 acts directly on vascular endothelial cells? Its high expression of the initial part of whether AS ox-LDL-induced endothelial injury? Based on these questions, we must first detect the IL-22 receptor in human vascular endothelial Cells. Experiment IL-22 receptor in human vascular endothelial expression of different concentrations of ox-LDL stimulation of cultured human umbilical vein endothelial cells (CRL1730) were collected different time (0h, 6h, 12h, 24h, 48h) experimental cells extraction of total RNA using real-time quantitative PCR was used to detect the relative expression levels of IL-22R1 mRNA; On the other hand, the use of PE-labeled anti-human IL-22R antibody extracellular staining cells were collected, and detection of the IL-22 receptor protein expression on the cell. CRL1730 cells express IL-22R, and its expression is influenced by ox-LDL concentration and stimulation time. 100μg/ml ox-LDL CRL1730 cells 24 hours after treatment, IL-22R-positive cells was significantly increased, and the difference was statistically significant (P lt; 0.01). Experiment two IL-22 ox-LDL stimulation of human umbilical vein endothelial cell molecule expression change on the part of the experimental validation of the vascular endothelial cell surface IL-22 receptor, and ox-LDL stimulation showed dynamic changes, then IL -22 on vascular endothelial cells, ox-LDL stimulated endothelial cells play what role? we first chose 7 and IL-22 function or endothelial cell damage is closely related to the gene expression of COX-2, PGES, MCP-1 , MMP1, ICAM, IL-6 and Bcl-2 expression of ox-LDL endothelial cells using RT-PCR and ELISA to detect the effect of IL-22 related molecules changes the role of IL-22 as an entry point to find target point, and then explore its mechanism in depth. Our study found that the addition of IL-22, the endothelial cells of ox-LDL Bcl-2 and ICAM expression were significantly higher (P lt; 0.01). Experiment three IL-22 ox-LDL-induced human umbilical vein endothelial cell apoptosis by Annexin V-PI apoptosis detection kit experiment, we found that adding IL-22 significantly inhibited the ox-LDL stimulation of endothelial cells withered death (P lt; 0.05); via real-time quantitative RT-PCR detection found that IL-22 to promote the anti-apoptotic gene Bcl-2, Bcl-xl and Bcl-w expression, and reduce Caspase3 mRNA expression (P lt; 0.05); Finally, we by Western Blot experiments found that the role of IL-22 cells within 1-2 hours STAT3 phosphorylation occurs four hours after the Bcl-2 protein expression was significantly elevated. Based on the above study, we hypothesized that IL-22 may be through the phosphorylation of STAT3, directly or indirectly raised the anti-apoptotic molecule Bcl-2, Bcl-xl and Bcl-w expression and inhibit the expression of pro-apoptotic molecules Caspase3, thereby inhibiting the ox- LDL-induced endothelial cell apoptosis. In summary, the study found that IL-22 is associated with coronary artery stenosis early lesions and its inhibition of apoptosis of the endothelial cells of the ox-LDL is particularly significant. IL-22 may be damaged through the regulation of apoptosis of endothelial cells to repair damaged endothelium and to maintain its integrity, and thus indirectly slowing the process of atherosclerosis.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease > Artery disease
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