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

Trinh, Hoang Kim Tu; Suh, Dong‐Hyeon; Nguyen, Thuy Van Thao; Choi, Youngwoo; Park, Hae‐Sim; Shin, Yoo Seob

doi:10.1016/j.plefa.2018.12.002

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…As in Figure 7 CysLTR1 to P2Y12R ratio in our previous study, 25 we combined Mon and Clo (Clo/Mon) at a ratio of 1:1. We used considerably lower doses of Mon and Clo (10 mg/kg for each drug) compared to previous experimental studies.…”

Section: Correlation Of Pea and Eosinophil Count With Inflammatory mentioning

confidence: 99%

“…These results are relevant because (a) lower concentrations of drugs were used; and (b) the secondary challenge in the eosinophilic asthma mouse model. Based on the CysLTR1 to P2Y12R ratio in our previous study, 25 we combined Mon and Clo (Clo/Mon) at a ratio of 1:1. We used considerably lower doses of Mon and Clo (10 mg/kg for each drug) compared to previous experimental studies.…”

Section: Correlation Of Pea and Eosinophil Count With Inflammatory mentioning

confidence: 99%

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The synergistic effects of clopidogrel with montelukast may be beneficial for asthma treatment

Trinh

Nguyen

Choi

et al. 2019

J Cellular Molecular Medi

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Platelets modulate asthma pathogenesis by forming the platelet‐eosinophil aggregation (PEA), which facilitates the activation of eosinophils. Platelets exhibit the purinergic receptor (P2Y12R), which responds to cysteinyl leukotriene E4 (LTE 4 ). We have suggested that the combination of an antiplatelet drug (clopidogrel, [Clo]) and montelukast (Mon) would synergistically suppress asthma. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) on days 0 and 14 and subsequently challenged on days 28‐30 and 42‐44. Mice were administered with Clo (10 mg/kg), Mon (10 mg/kg) or both drugs (Clo/Mon) orally 30 minutes before the OVA (1%) challenge on days 42‐44. Mice were assayed for airway hyper‐responsiveness (AHR) to methacholine and airway inflammation. Clopidogrel and montelukast attenuated the increased AHR; the combined treatment was more effective than a single treatment for total and eosinophil counts (all P < 0.05). Levels of interleukin (IL)‐4, IL‐5, IL‐13, platelet factor 4, eosinophil peroxidase and LTE 4 increased in the bronchoalveolar lavage fluid of asthmatic mice, but these levels decreased in mice treated with Clo/Mon (all P < 0.05). Goblet cell hyperplasia decreased in response to Clo/Mon. Mouse platelets and eosinophils were isolated and co‐cultured for an in vitro assay with 10 µmol/L adenosine diphosphate (ADP), LTE 4 (200 nmol/L), Mon (1 µmol/L), Clo (1 µmol/L) and Clo/Mon (1 µmol/L). Flow cytometry revealed that the increased formation of the PEA (%) was fully mediated by ADP and partly mediated by LTE 4 . Clo/Mon reduced ADP‐induced PEA formation and P‐selectin expression ( P < 0.05). In conclusion, Clo/Mon synergistically relieved asthma by inhibiting ADP‐mediated PEA formation.

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Section: Correlation Of Pea and Eosinophil Count With Inflammatory mentioning

confidence: 99%

Section: Correlation Of Pea and Eosinophil Count With Inflammatory mentioning

confidence: 99%

The synergistic effects of clopidogrel with montelukast may be beneficial for asthma treatment

Trinh

Nguyen

Choi

et al. 2019

J Cellular Molecular Medi

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“…Female BALB/c mice at 6 and 12 weeks old (weight 20 ± 2 and 21 ± 2 g, respectively) were purchased from the Jackson Laboratory (Bar Harbor, ME, USA), housed under specific pathogen-free conditions, maintained on a 12-h light/dark cycle and fed ad libitum. Asthma was induced at two time points, modified from a previous protocol 30 . Briefly, on days 0 and 14, mice were intraperitoneally sensitized with ovalbumin (OVA)/aluminum hydroxide (Alum) solution at 10 µg/1 mg. On days 28-30, the mice were challenged with 2% OVA for 30 min using an ultrasonic nebulizer (NE-SM1; Ktmed Inc., Seoul, South Korea).…”

Section: Establishment Of An Loa Mouse Modelmentioning

confidence: 99%

“…The BALF was centrifuged at 1200 revolutions per minute for 5 min at 4°C, and the supernatant was harvested and stored at −70°C until further experiments. Total and differential cell counts were determined by using a hemocytometer and hematoxylin-eosin (HE)-stained slides as previously described 30 .…”

Section: Analysis Of Differential Cell Count and Histologymentioning

confidence: 99%

Osteopontin contributes to late-onset asthma phenotypes in adult asthma patients

et al. 2020

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Patients with late-onset asthma (LOA) have poor clinical outcomes. Osteopontin (OPN) is associated with airway inflammation and remodeling. To investigate the role of OPN in LOA compared to early-onset asthma (EOA), serum OPN levels were compared between 131 adult asthma patients (48 LOA and 83 EOA patients) and 226 healthy controls (HCs). BALB/c mice were sensitized with ovalbumin with/without polyinosinic-polycytidylic acid (poly(I:C)) from week 6 (A6 mice) or week 12 (A12 mice) after birth. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), cell counts, histology, and Spp1 expression were assessed. The levels of OPN, transforming growth factor β1 (TGF-β1), chitinase 3-like 1 (CH3L1), and interleukin (IL) 5 were measured by ELISA. The expression of Smad3 phosphorylation and tissue transglutaminase 2 (TGM2) was evaluated by Western blot. The serum OPN levels were significantly higher in asthma patients than in HCs and in LOA patients than in those with EOA (P < 0.05) and were positively correlated with serum TGF-β1 and CH3L1 (r = 0.174, r = 0.264; P < 0.05). A12 mice showed elevated AHR with increased levels of OPN/TGF-β1/IL-5 in BALF and Spp1 compared to A6 mice. Poly(I:C) induced remarkable TGF-β1, CH3L1, Th2 cytokine, and OPN levels in BALF and the expression of phosphorylated Smad3, TGM2, and Spp1 in the lungs. OPN triggered TGF-β1/Smad3 signaling in the lungs, which was suppressed by dexamethasone and anti-IL5 antibody. In conclusion, aging and exposure to viral infections may induce OPN release and consequently modulate inflammation and TGF-β1/ Smad3-related remodeling, contributing to the development of LOA.

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“…OVAchallenged mice models have also been used to examine the role of CysLT receptors and leukotriene receptor antagonists in airway inflammation and modeling (Henderson et al, 2002;Ikeda et al, 2014). Interestingly, a few studies using gene knockout mice with OVA or leukotriene E 4 challenge have predicted additional leukotriene receptors that may be critical new drug targets for asthma, which are still under investigation (Paruchuri et al, 2009;Kanaoka et al, 2013;Trinh et al, 2019).…”

Section: Preclinical Models Of Asthmamentioning

confidence: 99%

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

Wendell¹,

Fan²,

Zhang³

2019

Pharmacol Rev

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

Cited by 11 publications

References 35 publications

The synergistic effects of clopidogrel with montelukast may be beneficial for asthma treatment

The synergistic effects of clopidogrel with montelukast may be beneficial for asthma treatment

Osteopontin contributes to late-onset asthma phenotypes in adult asthma patients

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

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