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Tissue Inhibitor of Metalloproteinase-1 Enhances Eosinophilic Airway Inflammation in Severe Asthma

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dc.contributor.authorCao, TBT-
dc.contributor.authorQuoc, QL-
dc.contributor.authorYang, EM-
dc.contributor.authorMoon, JY-
dc.contributor.authorShin, YS-
dc.contributor.authorRyu, MS-
dc.contributor.authorChoi, Y-
dc.contributor.authorPark, HS-
dc.date.accessioned2023-09-11T06:01:38Z-
dc.date.available2023-09-11T06:01:38Z-
dc.date.issued2023-
dc.identifier.issn2092-7355-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/26315-
dc.description.abstractPurpose: Severe asthma (SA) is characterized by persistent airway inflammation and remodeling, followed by lung function decline. The present study aimed to evaluate the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the pathogenesis of SA. Methods: We enrolled 250 adult asthmatics (54 with SA and 196 with non-SA) and 140 healthy controls (HCs). Serum TIMP-1 levels were determined by enzyme-linked immunosorbent assay. The release of TIMP-1 from airway epithelial cells (AECs) in response to stimuli as well as the effects of TIMP-1 on the activations of eosinophils and macrophages were evaluated in vitro and in vivo. Results: Significantly higher levels of serum TIMP-1 were noted in asthmatics than in HCs, in the SA group than in non-SA group, and in the type 2 SA group than in non-type 2 SA group (P < 0.01 for all). A negative correlation between serum TIMP-1 and FEV1% values (r = −0.400, P = 0.003) was noted in the SA group. In vitro study demonstrated that TIMP-1 was released from AECs in response to poly I:C, IL-13, eosinophil extracellular traps (EETs) and in coculture with eosinophils. TIMP-1-stimulated mice showed eosinophilic airway inflammation, which was not completely suppressed by steroid treatment. In vitro and in vivo functional studies showed that TIMP-1 directly activated eosinophils and macrophages, and induced the release of EETs and macrophages to polarize toward M2 subset, which was suppressed by anti-TIMP-1 antibody. Conclusions: These findings suggest that TIMP-1 enhances eosinophilic airway inflammation and that serum TIMP-1 may be a potential biomarker and/or therapeutic target for type 2 SA.-
dc.language.isoen-
dc.titleTissue Inhibitor of Metalloproteinase-1 Enhances Eosinophilic Airway Inflammation in Severe Asthma-
dc.typeArticle-
dc.identifier.pmid37075799-
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359643-
dc.subject.keywordairway remodeling-
dc.subject.keywordAsthma-
dc.subject.keywordeosinophils-
dc.subject.keywordepithelial cells-
dc.subject.keywordinflammation-
dc.subject.keywordmacrophages-
dc.subject.keywordTIMP-1-
dc.contributor.affiliatedAuthorShin, YS-
dc.contributor.affiliatedAuthorRyu, MS-
dc.contributor.affiliatedAuthorChoi, Y-
dc.contributor.affiliatedAuthorPark, HS-
dc.type.localJournal Papers-
dc.identifier.doi10.4168/aair.2023.15.4.451-
dc.citation.titleAllergy, asthma & immunology research-
dc.citation.volume15-
dc.citation.number4-
dc.citation.date2023-
dc.citation.startPage451-
dc.citation.endPage472-
dc.identifier.bibliographicCitationAllergy, asthma & immunology research, 15(4). : 451-472, 2023-
dc.identifier.eissn2092-7363-
dc.relation.journalidJ020927355-
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Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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