AI Article Synopsis
- Cysteinyl leukotrienes (CysLTs) are key players in allergic reactions, promoting mast cell (MC) activation through their Type 1 receptors (CysLT1R).
- The study utilized MC models to investigate the mechanisms of CysLT1R in MC activation, finding that the receptor significantly enhances IgE-mediated signaling pathways like Akt and ERK, ultimately increasing TNF-α production.
- Despite these findings, the use of shRNA to knock down CysLT1R indicated a more complex regulatory mechanism, suggesting that both rapid degranulation and delayed inflammatory mediator synthesis are co-regulated by CysLT1R during MC activation.
Article Abstract
Cysteinyl leukotrienes (CysLTs), released from mast cells (MCs), are important mediators in allergy. Type 1 receptors for CysLTs (CysLT1R) are involved in accelerating IgE-mediated MC activation. In this study, we aimed to elucidate the mechanisms underlying CysLT1R-mediated MC activation. The CysLT1R agonist/antagonist was applied to two types of major MC models-RBL-2H3 cells and bone marrow-derived MCs (BMMCs). The use of CysLT1R and CysLT2R inhibitors revealed that CysLT1R plays a major role in the acceleration of MC activation. The administration of the CysLT1R agonist leukotriene D4 upregulated IgE-mediated Akt and ERK phosphorylation and subsequently enhanced TNF-α expression, suggesting that CysLT1R regulates the downstream pathway of MC activation. However, these observations were not corroborated by CysLT1R knockdown using shRNA, suggesting a differential regulatory mechanism between the temporal and constitutive inhibitions of CysLT. In conclusion, CysLT1R enhances MC activation by accelerating IgE-induced signal transduction, which enables the co-regulation of rapid degranulation and delayed synthesis of inflammatory mediators in MCs.
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| http://dx.doi.org/10.1016/j.cellimm.2022.104632 | DOI Listing |
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