Open AccessShifting the Biosynthesis of Leukotrienes Toward Specialized Pro-Resolving Mediators by the 5-Lipoxygenase-Activating Protein (FLAP) Antagonist BRP-201
Author(s) -
Christian Kretzer,
Jordan PM,
Rossella Bilancia,
Antonietta Rossi,
Gür Maz T,
Erden Banoğlu,
Schubert US,
Oliver Werz
Publication year - 2022
Publication title -
journal of inflammation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 33
ISSN - 1178-7031
DOI - 10.2147/jir.s345510
Subject(s) - arachidonate 5 lipoxygenase , lipid signaling , lipoxygenase , inflammation , microbiology and biotechnology , proinflammatory cytokine , chemistry , antagonist , leukotriene , effector , receptor , enzyme , biochemistry , biology , immunology , arachidonic acid , asthma
Lipid mediators (LM) play crucial roles in the complex inflammation process with respect to initiation, maintenance, and resolution. Proinflammatory leukotrienes (LTs), generated by 5-lipoxygenase (LOX) and the 5-LOX-activating protein (FLAP), initiate and maintain inflammation while specialized pro-resolving mediators (SPMs) formed by various LOXs as key enzymes promote inflammation resolution and the return to homeostasis. Since 5-LOX also contributes to SPM biosynthesis, smart pharmacological manipulation of the 5-LOX pathway and accompanied activation of 12-/15-LOXs may accomplish suppression of LT formation but maintain or even elevate SPM formation. Here, we demonstrated that the FLAP antagonist BRP-201 possesses such pharmacological profile and causes a switch from LT toward SPM formation.