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Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma

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dc.contributor.authorKim, SH-
dc.contributor.authorJung, HW-
dc.contributor.authorKim, M-
dc.contributor.authorMoon, JY-
dc.contributor.authorBan, GY-
dc.contributor.authorKim, SJ-
dc.contributor.authorYoo, HJ-
dc.contributor.authorPark, HS-
dc.date.accessioned2022-10-28T05:28:49Z-
dc.date.available2022-10-28T05:28:49Z-
dc.date.issued2020-
dc.identifier.issn0105-4538-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/22442-
dc.description.abstractBACKGROUND: Asthma is associated with inflammatory dysregulation, but the underlying metabolic signatures are unclear. This study aimed to classify asthma inflammatory phenotypes based on cellular and metabolic features.

METHODS: To determine cellular and metabolic profiles, we assessed inflammatory cell markers using flow cytometry, sphingolipid (SL) metabolites using LC-MS/MS, and serum cytokines using ELISA. Targeted gene polymorphisms were determined to identify genetic predispositions related to the asthma inflammatory phenotype.

RESULTS: In total, 137 patients with asthma and 20 healthy controls (HCs) were enrolled. Distinct cellular and metabolic profiles were found between them; patients with asthma showed increased expressions of inflammatory cell markers and higher levels of SL metabolites compared to HCs (P < .05 for all). Cellular markers (CD66(+) neutrophils, platelet-adherent eosinophils) and SL metabolic markers (C16:0 and C24:0 ceramides) for uncontrolled asthma were also identified; higher levels were observed in uncontrolled asthma compared to controlled asthma (P < .05 for all). Asthmatics patients with higher levels of CD66(+) neutrophils had lower FEV1(%), higher ACQ (but lower AQLO) scores, and higher sphingosine and C16:0 ceramide levels compared to those with low levels of CD66(+) neutrophils. Asthmatics patients with higher levels of platelet-adherent eosinophils had higher S1P levels compared to those with lower levels of platelet-adherent eosinophils. Patients carrying TT genotype of ORMDL3 had more CD66(+) neutrophils; those with AG/ GG genotypes of SGMS1 exhibited higher platelet-adherent eosinophils.

CONCLUSION: Patients with uncontrolled asthma possess distinct inflammatory phenotypes including increased CD66(+) neutrophils and platelet-adherent eosinophils, with an imbalanced ceramide/S1P rheostat, potentially involving ORMDL3 and SGMS1 gene polymorphisms. Ceramide/S1P synthesis could be targeted to control airway inflammation.
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dc.language.isoen-
dc.subject.MESHAsthma-
dc.subject.MESHCeramides-
dc.subject.MESHChromatography, Liquid-
dc.subject.MESHEosinophils-
dc.subject.MESHHumans-
dc.subject.MESHLysophospholipids-
dc.subject.MESHPhenotype-
dc.subject.MESHSphingosine-
dc.subject.MESHTandem Mass Spectrometry-
dc.titleCeramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma-
dc.typeArticle-
dc.identifier.pmid32072647-
dc.subject.keywordasthma-
dc.subject.keywordceramide-
dc.subject.keywordneutrophil-
dc.subject.keywordplatelet-adherent eosinophil-
dc.subject.keywordsphingosine-1-phosphate-
dc.contributor.affiliatedAuthorKim, SH-
dc.contributor.affiliatedAuthorPark, HS-
dc.type.localJournal Papers-
dc.identifier.doi10.1111/all.14236-
dc.citation.titleAllergy-
dc.citation.volume75-
dc.citation.number8-
dc.citation.date2020-
dc.citation.startPage1991-
dc.citation.endPage2004-
dc.identifier.bibliographicCitationAllergy, 75(8). : 1991-2004, 2020-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1398-9995-
dc.relation.journalidJ001054538-
Appears in Collections:
Journal Papers > Hospital > Clinical Trial Center
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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