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CysLT 1 R regulates cys‐LT‐mediated calcium influx and oxidized LDL‐uptake in macrophages
Author(s) -
Pokhrel Sabita,
Duah Ernest,
Paruchuri Sailaja,
Thodeti Charles
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.489.6
Subject(s) - scavenger receptor , cd36 , receptor , chemistry , lipoprotein , microbiology and biotechnology , foam cell , monocyte , macrophage , inflammation , low density lipoprotein , cancer research , biology , biochemistry , immunology , cholesterol , in vitro
Cysteinyl leukotrienes (cys‐LTs), LTC 4 , LTD 4 , LTE 4 are potent inflammatory lipid mediators that act through two distinct G‐protein‐coupled receptors, CysLT 1 R and CysLT 2 R. Although cys‐LTs are shown to induce vascular leakage and atherosclerosis, the molecular mechanism by which cys‐LTs modulate endothelial and macrophage functions are not well understood. Atherosclerosis is the chronic inflammatory disease that accounts for the global epidemic of cardiovascular diseases (CVD), mainly driven by endothelial dysfunction. We have recently shown that cys‐LTs regulate endothelial cell (EC) dysfunction via CysLT 2 R, enhancing EC contraction and permeability. Further, cys‐LTs enhance TNFα‐mediated up‐regulation of VCAM‐1 and attachment of THP‐1 cells to endothelium. Therefore, we further focused on cys‐LT‐mediated effects in Raw and THP‐1‐derived macrophages. We observed that macrophages express mainly CysLT 1 R and flux calcium via CysLT 1 R in response to LTD 4 . Further, LTD 4 significantly promoted oxidized low density lipoprotein (ox‐LDL) uptake by macrophages. Importantly, LTD 4 treatment enhanced the expression of a scavenger receptor CD36, Oxidized low‐density lipoprotein receptor 1 (OLR1), Monocyte chemoattractant protein 1 (MCP1) and Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) transcripts suggesting that these receptors could mediate LTD 4 ‐induced ox‐LDL uptake by macrophages contributing to atherosclerosis. Support or Funding Information NIH R15 grant (1R15HL133918), and James Foght Professorship support. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .