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• W4362725982 abstract "Interactions between vascular endothelial cells and inflammatory leukocytes are intermediated via cell adhesion molecules and they become one of the key events for vascular cell injury and development of atherosclerosis. This study evaluated the effects of MTX-peptide conjugates as anti-inflammatory agents on human coronary artery endothelial cells (HCAEC) and Molt-3 T cells. Cyclic peptides, cLABL and cLBEL, were derived from the a- and b-subunits of leukocyte function-associated antigen-1 (LFA-1), respectively. They interact with intercellular adhesion molecule-1 (ICAM-1) to inhibit LFA-1/ICAM-1-mediated homotypic or heterotypic T-cell adhesion. cLABL and cLBEL were linked to the anti-inflammatory drug, methotrexate (MTX), to produce MTX-cLABL and MTX-cLBEL conjugates. This study showed that peptides and MTX-peptide conjugates inhibited T cell adhesion to HCAEC monolayers while MTX alone did not. The conjugates, but not MTX, inhibited binding of anti-ICAM-1 monoclonal antibody (mAb) to ICAM-1 on the HCAEC. This indicates that conjugation of MTX to cLABL and cLBEL peptides did not dramatically change their binding properties to ICAM-1. The conjugates had relatively lower toxicity to cells compared to MTX alone, while they were more toxic than the parent peptides. At low concentrations, MTX, MTX-cLABL and MTX-cLBEL decreased production of IL-6 and IL-8 as inflammatory cytokines. In contrast, higher concentrations of the parent peptides compared to the conjugates were required to inhibit IL-6 and IL-8 productions. Overall, both MTX-cLABL and MTX-cLBEL were more active than both free-peptides. In addition, the conjugates were less toxic than MTX alone. In conclusion, the conjugate can selectively target MTX to ICAM-1-expressing cells to increase cell targeting and to lower MTX toxicity." @default.
• W4362725982 created "2023-04-10" @default.
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• W4362725982 date "2023-01-01" @default.
• W4362725982 modified "2023-09-30" @default.
• W4362725982 title "Evaluation of LFA-1 Peptide-Methotrexate Conjugates in Modulating Endothelial Cell Inflammation and Cytokine Regulation" @default.
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• W4362725982 doi "https://doi.org/10.18103/mra.v11i2.3534" @default.
• W4362725982 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37063234" @default.
• W4362725982 hasPublicationYear "2023" @default.
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