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Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma

Authors
Trinh, HKT; Suh, DH; Nguyen, TVT; Choi, Y; Park, HS; Shin, YS
Citation
Prostaglandins, leukotrienes, and essential fatty acids, 141. : 17-23, 2019
Journal Title
Prostaglandins, leukotrienes, and essential fatty acids
ISSN
0952-32781532-2823
Abstract
Identification of the characterization of cysteinyl leukotrienes receptor (CysLTRs) could facilitate our understanding of these receptors' role in asthma. We aimed to investigate the localization and interactions of CysLTRs using a mouse model of asthma. BALB/c mice were administered ovalbumin (OVA) to induce allergic asthma. Some mice were administered the antagonists of CysLTR1, CysLTR2, and purinergic receptor P2Y12 (P2Y12R) (montelukast, HAMI 3379 and clopidogrel, respectively). The expression levels of CysLTR1, CysLTR2, and P2Y12R on lung tissues and inflammatory cells were evaluated by western blot, flow cytometry, and immunochemistry. CysLTR1 and P2Y12R were significantly up-regulated in lung tissues (P<0.05 for each) from mouse after being sensitized and challenged with OVA (OVA/OVA). The ratio of CysLTR1: CysLTR2: P2Y12R in lungs of negative control (NC) mice was shifted from 1:0.43:0.35 to 1:0.65:1.34 in OVA/OVA mice. Montelukast significantly diminished the up-regulation of CysLTR1, CysLTR2, and P2Y12R (P<0.05 for each), while the effects of HAMI 3379 and clopidogrel were predominant on the expression of CysLTR2 and P2Y12R, respectively. Montelukast predominantly diminished the cell count, while clopidogrel potently inhibited the release of interleukin (IL)-4, IL-5, and IL-13. Our study demonstrated the interactions between CysLTRs, thereby highlighting the potential synergistic effects of CysLTR antagonists in asthma treatment.
Keywords
AsthmaClopidogrelCysteinyl leukotrienes receptorMontelukast
MeSH terms
Acetates / pharmacologyAcetates / therapeutic useAnimalsAsthma / chemically inducedAsthma / drug therapyAsthma / metabolism*Clopidogrel / pharmacologyClopidogrel / therapeutic useCyclohexanecarboxylic Acids / pharmacologyDisease Models, AnimalDrug Therapy, CombinationEosinophils / drug effectsFemaleInflammation / drug therapyInterleukins / metabolismLeukotriene Antagonists / pharmacologyLeukotriene Antagonists / therapeutic useMiceMice, Inbred BALB COvalbumin / pharmacologyPhthalic Acids / pharmacologyPurinergic P2Y Receptor Antagonists / pharmacologyPurinergic P2Y Receptor Antagonists / therapeutic useQuinolines / pharmacologyQuinolines / therapeutic useReceptors, Leukotriene / metabolism*Receptors, Purinergic P2Y12 / metabolismTh2 Cells / drug effectsTh2 Cells / metabolism
DOI
10.1016/j.plefa.2018.12.002
PMID
30661601
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
AJOU Authors
박, 해심신, 유섭
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