Role of an indole-thiazolidiene PPAR pan ligand on actions elicited by G-protein coupled receptor activated neutrophils

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
José Roberto SantinSandra Helena Poliselli Farsky

Abstract

Neutrophils are the first line of defence during inflammatory processes; nevertheless, exacerbated influx and actions of neutrophils in terms of uncontrolled inflammation are harmful to the host. Hence, neutrophil activity is the target of drugs seeking to address undesired inflammation. Here, we investigated the mechanisms of action of a ligand of the three isoforms of peroxisome proliferator-activated receptors (PPAR; (5Z)-5-[(5-bromo-1H-indole-3-yl)methylene]-3-(4-chlorobenzyl)-thiazolidine-2,4-dione), dubbed LYSO-7, on neutrophils activated by N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP), an agonist of G-protein coupled receptors (GPCRs) that binds to membrane-formylated peptide and activates intracellular inflammation pathways. Neutrophils were collected from the peritoneal cavity of male Wistar rats four hours after oyster glycogen injection. Afterwards, the neutrophils were incubated with saline or LYSO-7 (1 or 10 μM, 30 min), washed and stimulated with fMLP (10-7 μM, 1 h). LYSO-7 treatment inhibited gene and protein expression of adhesion molecules, CD62 L and CD18, abolished adhesion of neutrophils to endothelial cells, impaired chemotaxis, blocked the enhancement of intracellular calcium levels, induced the ex...Continue Reading

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Oct 28, 2019·Reviews in Endocrine & Metabolic Disorders·Syeda Momna IshtiaqJunaid Ali Khan

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