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)
| Protein | Definition | Taxonomy |
|---|---|---|
| Plasminogen activator inhibitor 1 | A plasminogen activator inhibitor 1 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P05121] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| gallic acid | gallate : A trihydroxybenzoate that is the conjugate base of gallic acid. | trihydroxybenzoic acid | antineoplastic agent; antioxidant; apoptosis inducer; astringent; cyclooxygenase 2 inhibitor; EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor; geroprotector; human xenobiotic metabolite; plant metabolite |
| hexachlorophene | hexachlorophene : An organochlorine compound that is diphenylmethane in which each of the phenyl groups is substituted by chlorines at positions 2, 3, and 5, and by a hydroxy group at position 6. An antiseptic that is effective against Gram-positive organisms, it is used in soaps and creams for the treatment of various skin disorders. It is also used in agriculture as an acaricide and fungicide, but is not approved for such use within the European Union. Hexachlorophene: A chlorinated bisphenol antiseptic with a bacteriostatic action against Gram-positive organisms, but much less effective against Gram-negative organisms. It is mainly used in soaps and creams and is an ingredient of various preparations used for skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797) | bridged diphenyl fungicide; polyphenol; trichlorobenzene | acaricide; antibacterial agent; antifungal agrochemical; antiseptic drug |
| 1,2,5,8-tetrahydroxy anthraquinone | 1,2,5,8-tetrahydroxy anthraquinone: structure in first source quinalizarin : A tetrahydroxyanthraquinone having the four hydroxy groups at the 1-, 2-, 5- and 8-positions. | tetrahydroxyanthraquinone | EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor |
| epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
| sennoside A | sennoside A : A member of the class of sennosides that is rel-(9R,9'R)-9,9',10,10'-tetrahydro-9,9'-bianthracene-2,2'-dicarboxylic acid which is substituted by hydroxy groups at positions 4 and 4', by beta-D-glucopyranosyloxy groups at positions 5 and 5', and by oxo groups at positions 10 and 10'. The exact stereochemisty at positions 9 and 9' is not known - it may be R,R (as shown) or S,S. | oxo dicarboxylic acid; sennosides | |
| Epigallocatechin 3,5-Digallate | catechin | ||
| pai 039 | tiplaxtinin: inhibitor of plasminogen activator inhibitor-1 | indole-3-acetic acids | |
| xr 334 | XR 334: a low molecular weight modulator of human plasminogen activator inhibitor-1 activity; structure given in first source; RN given refers to (Z,Z)-isomer | ||
| sideroxylonal c | sideroxylonal C: formylated phloroglucinol from flowers of Eucalyptus albens; structure in first source |