scholarly journals Inhibition of the lncRNA Mirt1 Attenuates Acute Myocardial Infarction by Suppressing NF-κB Activation

2017 ◽  
Vol 42 (3) ◽  
pp. 1153-1164 ◽  
Author(s):  
Xiangrao Li ◽  
Jian Zhou ◽  
Kai Huang
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Inflammatory Cell ◽  
Cultured Cells ◽  
Cardiac Fibroblasts ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Inflammatory Factors ◽  
Cardiac Functions

Background/Aims: The expression of a novel lncRNA, myocardial infarction associated transcript 1(Mirt1), has been shown to be upregulated in acute myocardial infarction (AMI). However, the role of Mirt1 in AMI is not clear. Methods: In this study, we analyzed the level of Mirt1 in cardiomyocytes and cardiac fibroblasts in AMI mice. Moreover, adenovirus mediated knockdown of Mirt1 was employed to clarify its roles in AMI mice or cultured cardiac fibroblasts. The cardiac functions and infarct size of AMI mice were examined, and tissues and cultured cells were collected and processed for histology and biochemical examination. Results: We demonstrated that Mirt1 was mainly expressed in cardiac fibroblasts, and that knockdown of Mirt1 improved cardiac functions, decreased cardiomyocytes apoptosis and attenuated inflammatory cell infiltration in vivo. Furthermore, knockdown of Mirt1 in cardiac fibroblasts not only attenuated the apoptosis of cardiomyocytes, but also suppressed the migration of macrophages under hypoxia in vitro. NF-κB signaling pathway, activated under hypoxia, was also inhibited by Mirt1 knockdown in fibroblasts. Conclusions: Knockdown of Mirt1 attenuates AMI injury presumably by decreasing cardiomyocytes apoptosis and reducing inflammatory cell infiltration. These effects could be attributed, at least partly, to inhibition of the NF-κB pathway, resulting in decreased expression of inflammatory factors.

scholarly journals PECAM1 Combines With CXCR4 to Trigger Inflammatory Cell Infiltration and Pulpitis Progression Through Activating the NF-κB Signaling Pathway

2020 ◽  
Vol 8 ◽  
Author(s):  
Yonghong Liu ◽  
Zhiyong Zhang ◽  
Wenjing Li ◽  
Songbo Tian
Keyword(s):  
Signaling Pathway ◽  
Dental Pulp ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Bioinformatics Analyses ◽  
Protein Protein Interaction ◽  
Platelet Endothelial Cell Adhesion ◽  
Human Dental Pulp

Pulpitis is a frequent bacterially driven inflammation featured with the local accumulation of inflammatory products in human dental pulps. A GEO dataset GSE16134 comprising data of inflamed dental pulp tissues was used for bioinformatics analyses. A protein-protein interaction (PPI) analysis suggested that chemokine receptor 4 (CXCR4) owned a high correlation with platelet endothelial cell adhesion molecule-1 (PECAM1). A rat model with pulpitis was established, and lipopolysaccharide (LPS)-induced human dental pulp fibroblasts (HDPFs) were used for in vitro experiments. Then, high expression of PECAM1 and CXCR4 was validated in the inflamed dental pulp tissues in rats and in LPS-induced HDPFs. Either downregulation of PECAM1 or CXCR4 suppressed inflammatory cell infiltration in inflamed tissues as well as the inflammation and apoptosis of HDPFs. A transcription factor myocyte-enhancer factor 2 (MEF2C) was predicted and validated as a positive regulator of either PECAM1 or CXCR4, which activated the NF-κB signaling pathway and promoted pulpitis progression. To sum up, this study suggested that MEF2C transcriptionally activates PECAM1 and CXCR4 to activate the B-cell and NF-κB signaling pathways, leading to inflammatory cell infiltration and pulpitis progression.

scholarly journals Inosine reduces inflammation and improves survival in a murine model of colitis

2003 ◽  
Vol 284 (1) ◽  
pp. G138-G144 ◽  
Author(s):  
J. G. Mabley ◽  
P. Pacher ◽  
L. Liaudet ◽  
F. G. Soriano ◽  
G. Haskó ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Inflammatory Cell ◽  
Dextran Sulfate ◽  
Oral Treatment ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Cytokines And Chemokines ◽  
Naturally Occurring

Inosine, a naturally occurring purine formed from the breakdown of adenosine, has recently been shown to exert powerful anti-inflammatory effects both in vivo and in vitro. This study evaluated inosine as a potential therapy for colitis. Colitis was induced in mice by the administration of dextran sulfate sodium (DSS). Oral treatment with inosine was begun either before the onset of colitis or as a posttreatment once colitis was established. Evaluation of colon damage and inflammation was determined grossly (body wt, rectal bleeding), histologically, and biochemically (colon levels of MPO, MDA, and cytokines). DSS-induced colitis significantly increased inflammatory cell infiltration into the colon. DSS-induced colitis also increased colon levels of lipid peroxidation, cytokines, and chemokines. Inosine protected the colon from DSS-induced inflammatory cell infiltration and lipid peroxidation. Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis.

scholarly journals The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4596-4604 ◽  
Author(s):  
Marjo M. P. C. Donners ◽  
Linda Beckers ◽  
Dirk Lievens ◽  
Imke Munnix ◽  
Johan Heemskerk ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Collagenolytic Activity ◽  
Neointima Formation ◽  
Wild Type ◽  
Vessel Volume ◽  
Necrosis Factor

Abstract We investigated the role of CD40 and CD40L in neointima formation and identified the downstream CD40-signaling intermediates (tumor necrosis factor [TNF]–receptor associated factors [TRAF]) involved. Neointima formation was induced in wild-type, CD40−/−, CD40L−/−, and in CD40−/− mice that contained a CD40 transgene with or without mutations at the CD40-TRAF2,3&5, TRAF6, or TRAF2,3,5&6 binding sites. Compared with wild-type mice, CD40−/− mice showed a significant decrease in neointima formation with increased collagen deposition and decreased inflammatory cell infiltration. Neointima formation was also impaired in wild-type mice reconstituted with CD40−/− bone marrow. In vitro, the capacity of CD40−/− leukocytes to adhere to the endothelium was reduced. Ligated carotid arteries of CD40−/− mice showed a smaller total vessel volume and an impaired remodeling capacity, reflected by decreased gelatinolytic/collagenolytic activity. Comparable results were found in mice with defects in CD40-TRAF6 and CD40-TRAF 2/3/5&6 binding, but not in mice with defects in CD40-TRAF2/3&5 binding. Neointima formation and vascular remodeling in CD40-receptor–deficient mice is impaired, due to a decreased inflammatory cell infiltration and matrix-degrading protease activity, with CD40-TRAF6 signaling as the key regulator. This identifies the CD40-TRAF6 axis as a potential therapeutic target in vascular disease.

scholarly journals The Anti-Inflammatory and Antiapoptotic Effects of Nicorandil in Antisepsis Cardiomyopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jinshuai Lu ◽  
Fen Liu ◽  
Xia Yu ◽  
Likun Xu ◽  
Lingling Zhang
Keyword(s):  
Survival Rate ◽  
Sham Group ◽  
Inflammatory Cell ◽  
Troponin I ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Inflammatory Factors ◽  
Sham Operation ◽  
Septic Cardiomyopathy ◽  
Myocardial Cells

Objective. To observe the effect of nicorandil on septic rats and explore the possible mechanism of its myocardial protection, so as to provide theoretical basis for the treatment of septic cardiomyopathy. Methods. Sixty male clean SD rats were selected as the research objects and randomly divided into 3 groups by random number method: sham operation group (sham group), cecal ligation and perforation group (CLP group), nicorandil treatment group (nicorandil+CLP group). After the operation, the nicorandil group was pumped with nicorandil diluent 1 ml/h (2 mg/kg/h) with a micropump for 6 hours. The sham group and CLP group were pumped with the same amount of normal saline 1 ml/h for a total of 6 hours. After 24 hours, the survival of the rats in each group was observed. The expression of troponin I (cTnI), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) in the serum was detected. Then, the ventricle was harvested for the observation of the pathological changes of myocardium. Quantitative real-time polymerase chain reaction and immunostaining were used to detect myocardial tissue apoptosis, and Western blot methods were used to detect protein expression changes in nuclear factor-κB (NF-κB) pathways. Results. 24 hours after operation, the survival rate of the rats in the CLP group was 60%. There was a large amount of necrosis of myocardial cells and inflammatory cell infiltration. The survival rate of rats in the nicorandil+CLP group was 75%. Compared with the CLP group, the necrosis of myocardial cells was reduced, and there was still a small amount of inflammatory cell infiltration. In the CLP group, myocardial inflammation and apoptosis were significant, and NF-κB pathway was activated. On the contrary, the NF-κB pathway in the nicorandil+CLP group was inhibited, and the expression of inflammatory factors and apoptosis factors was inhibited. Conclusion. Nicorandil can reduce the release of inflammatory factors in septic rats, improve the inflammatory response, reduce myocardial damage, and play a myocardial protective effect. Its mechanism may be related to the inhibition of the activation of NF-κB signaling pathway.

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