Leukotriene E4

Leukotriene E4 (LTE4) is a stable final metabolite of cysteinyl leukotrienes, produced by immune cells such as mast cells and eosinophils. Leukotriene E4 serves as a key biomarker for evaluating asthma severity, Aspirin (HY-14654) sensitivity, and mast cell activation disorders. Leukotriene E4 is a full functional agonist of CysLT₁R, which induces sustained intracellular calcium mobilization and Erk phosphorylation. Leukotriene E4 mediates inflammation in a P2Y₁₂ receptor-dependent manner. Leukotriene E4 can be used in the research of asthma and non-steroidal anti-inflammatory drug-exacerbated respiratory diseases^[1][2][3]. In Vitro:Leukotriene E4 induces concentration-dependent sustained intracellular calcium mobilization in LAD2 human mast cells, with an EC₅₀ of 1.67 nM^[1].
Leukotriene E4 induces only a very weak, non-sustained intracellular calcium mobilization response in LUVA human mast cells, with no detectable EC₅₀^[1].
Leukotriene E4 induces concentration-dependent intracellular calcium mobilization in HEK293T cells transfected with CYSLTR1, with an EC₅₀ of 83.2 nM^[1].
Leukotriene E4 (100 nM; 2-60 min) induces sustained phosphorylation of Erk in LAD2 human mast cells, and the activation signal remains detectable after 60 minutes^[1].
Leukotriene E4 (100 nM; 2-60 min) induces transient phosphorylation of Erk in LUVA human mast cells, with no sustained activation observed within 60 minutes^[1].
Leukotriene E4 (1-100 nM; 15 min) induces PTX-sensitive, MK571-resistant ERK phosphorylation in Chinese hamster ovary cells stably expressing human P2Y₁₂ receptors, with activation initiating at 1 nM and reaching a plateau at 100 nM^[2].
Leukotriene E4 (500 nM) induces calcium influx in LAD2 human mast cells, and this response is not inhibited by the P2Y₁₂ antagonist 2-MesAMP (HY-125989)^[2].
Leukotriene E4 (100 nM) induces the production of PGD₂ in the human mast cell line LAD2, and the generation of this product is completely dependent on the P2Y₁₂ receptor^[2].
Leukotriene E4 (1 μM; 10 min) does not induce the expression of CD62P (an activation marker) in human blood platelets^[2].
Leukotriene E4 (100 nM; 2-6 h) induces the expression of CCL4 and CSF2 mRNA and protein in LAD2 human mast cells via a CysLT1-dependent mechanism, with potency equivalent to or stronger than that of LTD4^[1].
Leukotriene E4 (100 nM; 2-6 h) induces only extremely weak CCL4 mRNA and protein expression in LUVA human mast cells, with much lower potency relative to LTD4^[1].
The induction of CCL4 mRNA expression in human mast cell line LAD2 by Leukotriene E4 (100 nM; 2 h) depends on the MEK/Erk pathway and intracellular/extracellular Ca²⁺, but is independent of Gi/o proteins or the PPAR-γ signaling pathway^[1].
Leukotriene E4 (100 nM; 5 min-2 h) requires prolonged exposure (2 h) to induce full CCL4 mRNA expression in LAD2 human mast cells, whereas short-term exposure (5 min) only elicits weak activity^[1].
Leukotriene E4 (100-500 nM; 6 h) induces high levels of MIP-1β production in LAD2 human mast cells, and this production process is mainly dependent on the P2Y₁₂ receptor; the P2Y₁₂ antagonist 2-MesAMP inhibits more than 50% of its production, while P2Y₁₂ shRNA knockdown almost completely blocks this production process^[2]. In Vivo:Leukotriene E4 (2.2 nmol; intranasal administration; once daily for 3 consecutive days) significantly enhances allergen-induced pulmonary eosinophilia, bronchovascular inflammation, and goblet cell metaplasia in sensitized BALB/c mice^[2].
Leukotriene E4 (2.2 nmol; intranasal administration; once daily for 3 consecutive days) enhances allergen-induced pulmonary inflammation in wild-type C57BL/6 mice, but this activity is significantly attenuated in mice lacking the P2Y₁₂ receptor^[2].
Leukotriene E4 (2.2 nmol; intranasal administration; once daily for 3 consecutive days) enhances allergen-induced pulmonary inflammation in BALB/c mice, and this effect is independent of the classical CysLT₁R and CysLT₂R receptors^[2].
The enhanced allergen-induced pulmonary inflammation effect in sensitized BALB/c mice mediated by Leukotriene E4 (2.2 nmol; intranasal administration; once daily for 3 consecutive days) is completely dependent on platelets^[2].