Dataset Information

Monocyte-Derived miRNA-1914-5p Attenuates IL-1β-Induced Monocyte Adhesion and Transmigration.

ABSTRACT: Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1β-induced ICAM-1 expression and monocyte adhesion to endothelial cells. However, whether monocyte miR-1914-5p affects monocyte recruitment is unclear. In this study, IL-1β decreased miR-1914-5p expression in a human monocyte cell line. Moreover, miR-1914-5p inhibition enhanced adhesion to endothelial cells with the upregulation of macrophage-1 antigen (Mac-1), a counter-ligand to ICAM-1. Transmigration through the endothelial layer was also promoted with the upregulation of monocyte chemotactic protein-1 (MCP-1). Furthermore, a miR-1914-5p mimic suppressed IL-1β-induced monocyte adhesion and transmigration in monocytes with Mac-1 and MCP-1 downregulation. Further investigation of miR-1914-5p in monocytes could lead to the development of novel diagnostic markers and therapeutic strategies for atherosclerosis.

SUBMITTER: Toriuchi K

PROVIDER: S-EPMC9917334 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Monocyte-Derived miRNA-1914-5p Attenuates IL-1β-Induced Monocyte Adhesion and Transmigration.

Toriuchi Kohki K Kihara Toshie T Aoki Hiromasa H Kakita Hiroki H Takeshita Satoru S Ueda Hiroko H Inoue Yasumichi Y Hayashi Hidetoshi H Shimono Yohei Y Yamada Yasumasa Y Aoyama Mineyoshi M

International journal of molecular sciences 20230201 3

Atherosclerosis can lead to cardiovascular and cerebrovascular diseases. Atherosclerotic plaque formation is promoted by the accumulation of inflammatory cells. Therefore, modulating monocyte recruitment represents a potential therapeutic strategy. In an inflammatory state, the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) is upregulated in endothelial cells. We previously reported that miR-1914-5p in endothelial cells suppresses interleukin (IL)-1β-induced ...[more]

PMID: 36769149

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Project description:IntroductionThe use of cardiopulmonary bypass (CPB) can induce sterile systemic inflammation that contributes to morbidity and mortality, especially in children. Patients have been found to have increased expression of cytokines and transmigration of leukocytes during and after CPB. Previous work has demonstrated that the supraphysiologic shear stresses existing during CPB are sufficient to induce proinflammatory behavior in non-adherent monocytes. The interactions between shear stimulated monocytes and vascular endothelial cells have not been well studied and have important translational implications. With these studies, we tested the hypothesis that non-physiological shear stress experienced by monocytes during CPB affects the integrity and function of the endothelial monolayer.MethodsWe have used an in vitro CPB model to study the interaction between THP-1 monocyte-like cells and human neonatal dermal microvascular endothelial cells (HNDMVECs). THP-1 cells were sheared in polyvinyl chloride (PVC) tubing at 2.1 Pa, twice of the physiological shear stress, for 2 h. ELISA, adhesion and transmigration assays, qPCR, and RNA silencing were used to assess the interactions between THP-1 cells and HNDMVECs were characterized after co-culture.ResultsWe found that sheared THP-1 cells adhered to and transmigrated through the HNDMVEC monolayer more readily than static THP-1 controls. Sheared THP-1 cells disrupted the VE-cadherin and led to the reorganization of cytoskeletal F-actin of HNDMVECs. A higher level of IL-8 was detected in the sheared THP-1 and HNDMVEC co-culture medium compared to the static THP-1 and HNDMVEC medium. Further, treating HNDMVECs with IL-8 resulted in increased adherence of non-sheared THP-1 cells, and upregulation in HNDMVECs of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1). Finally, inhibition of HNDMVECs CXCR2/IL-8 receptor with Reparixin and of IL-8 expression with siRNA blocked sheared THP-1 cell adhesion to the endothelial monolayer.ConclusionsThese results suggest that CPB-like sheared monocytes promote IL-8 production followed by increased endothelium permeability, and monocyte adhesion and transmigration. This study revealed a novel mechanism of post-CPB inflammation and will contribute to the development of targeted therapeutics to prevent and repair the damage to neonatal patients.

Project description:We investigated the hypothesis that transmigration drives monocyte transcriptional changes. Using Agilent Whole Human Genome Microarrays, we identified over 600 differentially expressed genes (2x, p<0.05) in freshly isolated human monocytes following 1.5 h of transmigration across IL1beta-stimulated ECs compared to untreated monocytes. Genes up-regulated by monocyte transmigration belong to a number of overrepresented functional groups including immune response, and inhibition of apoptosis. qRT-PCR confirmed increased expression of monocyte chemotactic proteins 1 and 3 and of NLR family apoptosis inhibitory protein (NAIP) following monocyte transmigration. In addition, quantification of annexin V binding revealed a reduction in apoptosis following monocyte transmigration. Comparison of gene expression in transmigrated monocytes to additional controls (monocytes which failed to transmigrate and monocytes incubated beneath stimulated ECs) revealed 89 differentially expressed genes which were controlled by the physical process of diapedesis. Functional annotation of these genes showed down-regulation of antimicrobial genes (e.g. alpha-defensin down 50x, cathelicidin down 9x, and cathepsin G down 3x). qRT-PCR confirmed down-regulation of these genes. Immunoblots confirmed that monocyte transmigration down-regulates alpha-defensin protein expression. Overall, these data indicate that exposure of monocytes to stimulated ECs promotes further monocyte recruitment and inhibits monocyte apoptosis. Unexpectedly, following transmigration monocytes displayed reduced anti-microbial expression. Monocytes were allowed to transmigrate across IL1b stimulated HUVEC. Monocytes which transmigrated and monocytes which failed to transmigrate were collected after 1.5 hours from 3 experimental replicates of different human donors. Untreated monocytes were collected as a control from 4 human donors. Monocytes incubated beneath stimulated HUVEC for 1.5 hours were also collected from four human donors as a control.

Dataset Information

Monocyte-Derived miRNA-1914-5p Attenuates IL-1β-Induced Monocyte Adhesion and Transmigration.

Publications

Monocyte-Derived miRNA-1914-5p Attenuates IL-1β-Induced Monocyte Adhesion and Transmigration.

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