Prostaglandin D2 inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP1 receptors

Säfholm, Jesper; Abma, Willem; Liu, Jielu; Balgoma, David; Fauland, Alexander; Kolmert, Johan; Wheelock, Craig E.; Adner, Mikael; Dahlén, Sven‐Erik

doi:10.1016/j.ejphar.2021.174282

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…Based on the DEGs of high-risk patients, the cMAP database identified different small molecules that may be effective in asthma, predominantly prostaglandin receptor agonists. Some studies found that prostaglandin D2 inhibits mediator release and antigen-induced bronchoconstriction in the guinea pig trachea by the activation of DP 1 receptors ( 59 ). Transgenic mice overexpressing the PGE 2 receptor EP 2 on mast cells show protective phenotype in allergic asthma models ( 60 ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

et al. 2022

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BackgroundAutophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking.MethodsClustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments.ResultsA total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model.ConclusionAutophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.

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Section: Discussionmentioning

confidence: 99%

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

et al. 2022

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“…For example, in vitro treatment with PGD 2 or BW 245C, a selective DP1 agonist, inhibited several inflammatory responses, including tumor necrosis factor-α-induced migration of Langerhans cells ( Angeli et al, 2001 ), and virus-induced inflammasome activation in Cd11b + cells ( Vijay et al, 2017 ). PGD 2 /DP1 signaling was also shown to suppress the production of interferon γ by NK T cells ( Torres et al, 2008 ), and histamine and leukotrienes by rings of the trachea ( Safholm et al, 2021 ). Furthermore, activation of the PGD 2 /DP1 pathway decreased the expression of IL-12 and upregulated the expression the anti-inflammatory cytokine IL-10 in dendritic cells ( Gosset et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage

Najar,

Alsabri,

Guedi

et al. 2023

Front. Cell Dev. Biol.

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D prostanoid receptor 1 (DP1), a prostaglandin D2 receptor, plays a central role in the modulation of inflammation and cartilage metabolism. We have previously shown that activation of DP1 signaling downregulated catabolic responses in cultured chondrocytes and was protective in mouse osteoarthritis (OA). However, the mechanisms underlying its transcriptional regulation in cartilage remained poorly understood. In the present study, we aimed to characterize the human DP1 promoter and the role of DNA methylation in DP1 expression in chondrocytes. In addition, we analyzed the expression level and methylation status of the DP1 gene promoter in normal and OA cartilage. Deletion and site-directed mutagenesis analyses identified a minimal promoter region (−250/−120) containing three binding sites for specificity protein 1 (Sp1). Binding of Sp1 to the DP1 promoter was confirmed using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Treatment with the Sp1 inhibitor mithramycin A reduced DP1 promoter activity and DP1 mRNA expression. Inhibition of DNA methylation by 5-Aza-2′-deoxycytidine upregulated DP1 expression, and in vitro methylation reduced the DP1 promoter activity. Neither the methylation status of the DP1 promoter nor the DP1 expression level were different between normal and OA cartilage. In conclusion, our results suggest that the transcription factor Sp1 and DNA methylation are important determinants of DP1 transcription regulation. They also suggest that the methylation status and expression level of DP1 are not altered in OA cartilage. These findings will improve our understanding of the regulatory mechanisms of DP1 transcription and may facilitate the development of intervention strategies involving DP1.

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Irisin Relaxes Rat Trachea via K_V Channels, K_ATP Channels, and BK_Ca Channels

Demirel

Özyener

2022

PPL

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Background/Objective: This study was aimed to investigate the effects of irisin on rat tracheal smooth muscle contraction-relaxation responses and the roles of voltage-gated potassium (KV) channels, ATP-sensitive potassium (KATP) channels, and large-conductance calcium-activated potassium (BKCa) channels in these effects. Methods: Isometric contraction and relaxation responses of tracheal segments were measured using the tissue bath method. Submaximal contractions were induced by ACh (10-5 M) or KCl (60 mM), and then concentration-response curves of irisin (10-9 to 10-6 M) were obtained. For the temporal control, a double-distilled water group was formed. ACh and irisin were added to the baths after tracheal segments were incubated with 4-AP (KV channel blocker), glibenclamide (KATP channel blocker), TEA, and iberiotoxin (BKCa channel blockers) to assess the role of K+ channels. In addition, a vehicle group was performed for the solvent dimethyl sulfoxide (DMSO). Results: Irisin exhibited the relaxant effects in tracheal segments precontracted with both ACh and KCl at concentrations of 10-8-10-6 M (p<0.05). Besides, incubations of 4-AP, glibenclamide, TEA, and iberiotoxin significantly inhibited the irisin-mediated relaxation (p<0.05), whereas DMSO incubation did not modulate irisin responses (p>0.05). Conclusion: In conclusion, the first physiological results on the relaxant effects of irisin in rat trachea were obtained. Our findings demonstrated that irisin mediates concentration-dependent relaxation in rat tracheas. Moreover, the present study reported for the first time that irisin-induced bronchorelaxation is associated with the K+ channels activity.

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Prostaglandin D2 inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP1 receptors

Cited by 4 publications

References 27 publications

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage

Irisin Relaxes Rat Trachea via K_V Channels, K_ATP Channels, and BK_Ca Channels

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Prostaglandin D2 inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP1 receptors

Cited by 4 publications

References 27 publications

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage

Irisin Relaxes Rat Trachea via KV Channels, KATP Channels, and BKCa Channels

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Irisin Relaxes Rat Trachea via K_V Channels, K_ATP Channels, and BK_Ca Channels