Dataset Information

Enhanced inflammasome activation and reduced sphingosine-1 phosphate S1P signalling in a respiratory mucoobstructive disease model.

ABSTRACT:

Background

Inflammasomes and sphingosine-1-phosphate (S1P) signalling are increasingly subject to intensive research in human diseases. We hypothesize that in respiratory muco-obstructive diseases, mucus obstruction enhances NLRP3 inflammasome activation and dysregulated S1P signalling.

Methods

Lung tissues from mice overexpressing the beta-unit of the epithelial sodium channel (?ENaC) and their littermate controls were examined by histology, immunofluorescence and confocal microscopy, followed by ImageJ quantitative analysis.

Results

Lower airways in ?ENaC mice showed patchy patterns of mucus obstruction and neutrophil-dominant infiltrations. In contrast to a ubiquitous distribution of TNF? specks, significantly (p?2?=?0.640; p?p?p?ConclusionThese results support that mucus obstruction may enhance NLRP3 inflammasome activation and dysregulated S1P signaling.

SUBMITTER: Tran HB

PROVIDER: S-EPMC7175514 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Enhanced inflammasome activation and reduced sphingosine-1 phosphate S1P signalling in a respiratory mucoobstructive disease model.

Tran Hai B HB Macowan Matthew G MG Abdo Adrian A Donnelley Martin M Parsons David D Hodge Sandra S

Journal of inflammation (London, England) 20200421

<h4>Background</h4>Inflammasomes and sphingosine-1-phosphate (S1P) signalling are increasingly subject to intensive research in human diseases. We hypothesize that in respiratory muco-obstructive diseases, mucus obstruction enhances NLRP3 inflammasome activation and dysregulated S1P signalling.<h4>Methods</h4>Lung tissues from mice overexpressing the beta-unit of the epithelial sodium channel (βENaC) and their littermate controls were examined by histology, immunofluorescence and confocal micros ...[more]

PMID: 32336954

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Project description:Because sphingosine 1-phosphate (S1P) is a potent stimulator of angiogenesis, we hypothesized that the S1P pathway is activated to stimulate endometrial/placental angiogenesis during pregnancy. We initially localized S1P signaling pathway members in the gravid and nongravid uterine horns of unilaterally pregnant ewes. Sphingosine kinase-1 expression was greater in gravid compared to nongravid horns. In situ hybridization revealed elevated expression of sphingosine 1-phosphate phosphatase (SGPP1) in gravid interplacentomal endometrial stroma on Days 20 and 40 compared to the nongravid uterine horn, but expression increased in endometrium of the nongravid uterine horn between Days 40 and 120. SGPP1 expression increased in placentomes late in gestation. Sphingosine 1-phosphate lyase mRNA was modestly expressed at Day 20 and then decreased. In contrast, sphingosine 1-phosphate receptor 1 (S1PR1) mRNA increased in endometrium and caruncular stroma of the gravid uterine horn. Treatment with FTY720 and VPC23019, S1P receptor antagonists, blocked human and ovine endothelial cell invasion using an in vitro model of sprouting angiogenesis. Knockdown of S1PR1 with siRNA reduced invasion responses as well. We previously reported that delta-like 4 (DLL4) and A disintegrin and metalloproteinase with thrombospondin-like repeats 1 (ADAMTS1) participate in endothelial cell invasion stimulated by S1P and growth factors in vitro, and thus investigated whether their expression correlated with areas undergoing angiogenesis in vivo. DLL4 expression was similar to S1PR1, while ADAMTS1 mRNA was expressed by endometria of both nongravid and gravid horns, as well as conceptus and placentomes. These results establish that S1P signaling pathway members and S1P- and growth factor-regulated genes are prominent in uterine and placental tissue and in some cases are correlated with areas undergoing angiogenesis. Thus, S1P signaling may be crucial for proper fetal-placental development.

Dataset Information

Enhanced inflammasome activation and reduced sphingosine-1 phosphate S1P signalling in a respiratory mucoobstructive disease model.

Background

Methods

Results

Publications

Enhanced inflammasome activation and reduced sphingosine-1 phosphate S1P signalling in a respiratory mucoobstructive disease model.

Similar Datasets

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