Dataset Information

Endothelial Cell Focal Adhesion Regulates Transendothelial Migration and Subendothelial Crawling of T Cells.

ABSTRACT: Leukocytes circulating in the blood stream leave out of blood vessels and infiltrate into inflamed tissues to perform immune responses. Endothelial cells (ECs) lining interior of the post-capillary venules regulate various steps of leukocyte extravasation. In response to inflammatory signals, ECs upregulate adhesion molecules and produce/present chemokines to support firm adhesion and intraluminal crawling of leukocytes. They also remodel junctions to facilitate leukocyte transendothelial migration (TEM). While roles of apical/lateral components of EC layers in regulating leukocyte extravasation have been extensively investigated, relatively little attention has been paid to the basal part of EC layers comprising subendothelial spaces. In this study, we employed interference reflection microscopy (IRM), a microscopy technique specialized for label-free visualization of cell-substrate contact, to study detailed dynamic interactions between basal part of ECs and T cells underneath EC monolayer. For TEM, T cells on EC monolayer extended protrusions through junctions to explore subendothelial spaces, and EC focal adhesions (EC-FAs) acted as physical barrier for the protrusion. Therefore, preferential TEM occurred through junctions where near-junction focal adhesion (NJ-FA) density of ECs was low. After TEM, T cells performed subendothelial crawling (SEC) with flattened morphology and reduced migration velocity due to tight confinement. T cell SEC mostly occurred through gaps formed in between EC-FAs with minimally breaking EC-FAs. Tumor necrosis factor-? (TNF-?) treatment significantly loosened confinement in subendothelial spaces and reduced NJ-FA density of ECs, thus remodeled basal part of EC layer to facilitate leukocyte extravasation.

SUBMITTER: Lee J

PROVIDER: S-EPMC5810271 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Endothelial Cell Focal Adhesion Regulates Transendothelial Migration and Subendothelial Crawling of T Cells.

Lee Jaehyun J Song Kwang Hoon KH Kim Taeyeob T Doh Junsang J

Frontiers in immunology 20180124

Leukocytes circulating in the blood stream leave out of blood vessels and infiltrate into inflamed tissues to perform immune responses. Endothelial cells (ECs) lining interior of the post-capillary venules regulate various steps of leukocyte extravasation. In response to inflammatory signals, ECs upregulate adhesion molecules and produce/present chemokines to support firm adhesion and intraluminal crawling of leukocytes. They also remodel junctions to facilitate leukocyte transendothelial migrat ...[more]

PMID: 29472915

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Project description:Gastric cancer (GC) is a prevalent cancer, which remains incurable, and therefore requires an alternative treatment method. Celecoxib is a nonsteroidal anti-inflammatory drug that targets cyclooxygenase-2, and exhibits anticancer effects. The present study aimed to investigate the anti-GC mechanism of celecoxib using bioinformatics methods. Gene expression datasets GSE56807 (GC tissues and normal gastric tissues) and GSE54657 (celecoxib-treated and non-treated human GC epithelial AGS cells) were downloaded from the Gene Expression Omnibus database. Two groups of differentially expressed genes (DEGs) were identified using limma package in R language. The criterion for GSE56807 was a false discovery rate of <0.05, while that for GSE54657 was P<0.01. Overlapping DEGs from the two datasets were screened out. Subsequently, pathway enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery software (P<0.1; gene count ?2). In addition, the protein-protein interactions (PPIs) among the overlapped DEGs were obtained based on IntAct, Database of Interacting Proteins, Biomolecular Interaction Network Database and Human Protein Reference Database. Finally, a PPI network was visualized using Cytoscape software. A total of 137 overlapped DEGs were obtained, and DEGs with opposite regulation directions in the two datasets were significantly enriched in focal adhesion and leukocyte transendothelial migration. Subsequently, a PPI network of overlapped DEGs was constructed. Comprehensively, a total of 8 key DEGs [cysteine and glycine rich protein 1 (CSRP1), thrombospondin 1 (THBS1), myosin light chain 9 (MYL9), filamin A (FLNA), actinin alpha 1 (ACTN1), vinculin (VCL), laminin subunit gamma 2 (LAMC2) and claudin 1 (CLDN1)] were upregulated in GC tissues and downregulated in celecoxib-treated cells. In conclusion, celecoxib may exhibit anti-GC effects by suppressing the expression of CSRP1, THBS1, MYL9, FLNA, ACTN1, VCL, LAMC2 and CLDN1, and inhibiting leukocyte transendothelial migration and focal adhesion. However, relevant experiments are required to confirm the conclusion of the present study.

Dataset Information

Endothelial Cell Focal Adhesion Regulates Transendothelial Migration and Subendothelial Crawling of T Cells.

Publications

Endothelial Cell Focal Adhesion Regulates Transendothelial Migration and Subendothelial Crawling of T Cells.

Similar Datasets

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