positive regulation of leukotriene production involved in inflammatory response

Definition

Target type: biologicalprocess

Any process that increases the rate, frequency or extent of the synthesis or release of any leukotriene following a stimulus as part of an inflammatory response. [GOC:bf]

Positive regulation of leukotriene production is a crucial step in the inflammatory response, a complex biological process triggered by tissue damage or infection. Leukotrienes are potent lipid mediators derived from arachidonic acid, a fatty acid found in cell membranes. The synthesis of leukotrienes is catalyzed by the enzyme 5-lipoxygenase (5-LO), which is tightly regulated to ensure appropriate inflammatory responses.

The process begins with the activation of immune cells, such as mast cells, macrophages, and neutrophils, upon encountering pathogens or tissue damage. This activation triggers a cascade of intracellular signaling events leading to the release of phospholipase A2 (PLA2). PLA2 hydrolyzes membrane phospholipids, releasing arachidonic acid, the precursor for leukotriene production.

Arachidonic acid is then channeled into the 5-LO pathway, where it undergoes a series of enzymatic steps. 5-LO, localized to the nuclear membrane, requires the presence of a calcium-dependent protein, 5-LO-activating protein (FLAP), to access its substrate. FLAP acts as a molecular chaperone, bringing arachidonic acid into close proximity with 5-LO, facilitating the initial step of leukotriene synthesis.

5-LO converts arachidonic acid to leukotriene A4 (LTA4), an unstable intermediate. LTA4 is then rapidly converted into various biologically active leukotrienes, including LTB4, LTC4, LTD4, and LTE4, by different enzymes.

LTB4, a potent chemoattractant, is involved in the recruitment and activation of neutrophils and other inflammatory cells to the site of inflammation. LTB4 also promotes leukocyte adhesion to the endothelium, facilitating their migration from the blood vessels into the inflamed tissue.

LTC4, LTD4, and LTE4, collectively known as cysteinyl leukotrienes, are potent bronchoconstrictors and contribute to the development of asthma and other respiratory disorders. They also induce vasoconstriction and increase vascular permeability, leading to edema formation.

Overall, the positive regulation of leukotriene production involves a complex interplay of enzymes, signaling pathways, and cellular responses. It is a critical step in the inflammatory response, orchestrating the recruitment of immune cells, the release of inflammatory mediators, and the development of various inflammatory symptoms. By understanding the molecular mechanisms underlying leukotriene production, researchers are striving to develop targeted therapies for inflammatory diseases.'
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Proteins (1)

Compounds (9)