5-/12-Lipoxygenase-linked cascade contributes to the IL-33-induced synthesis of IL-13 in mast cells, thus promoting asthma development
DC Field | Value | Language |
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dc.contributor.author | Ro, MyungJa | - |
dc.contributor.author | Lee, A-Jin | - |
dc.contributor.author | Kim, Jae-Hong | - |
dc.date.accessioned | 2021-09-02T15:52:55Z | - |
dc.date.available | 2021-09-02T15:52:55Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2018-02 | - |
dc.identifier.issn | 0105-4538 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/77849 | - |
dc.description.abstract | Background: As asthma progresses, the levels of IL-33 in serum are markedly increased and contribute to asthmatic development and exacerbation. Mast cells, one of the principal effector cells in the pathogenesis of asthma, express high levels of the IL-33 receptor ST2 and have been shown to be activated by IL-33. Thus, IL-33 stimulates mast cells to produce Th2-type cytokines such as IL-13, thus contributing to asthmatic development. However, the signaling mechanism for IL-33-induced synthesis of Th2 cytokines, particularly IL-13, has not been fully elucidated in mast cells. Methods: The role of 5- or 12-LO in the IL-33-induced synthesis of IL-13 was investigated using knockdown or pharmacological inhibitors in bone marrow-derived mast cells (BMMCs) and animal model. Results: Blockade of 5- or 12-LO significantly suppressed IL-33-induced synthesis of IL-13 in BMMCs. The subsequent action of 5- and 12-LO metabolites through their specific receptor, BLT2, was also critical for IL-33-induced synthesis of IL-13. We also demonstrated that the MyD88-p38 kinase cascade lies upstream of 5-/12-LO and that NF-kappa B lies downstream of 5-/12-LO to mediate the IL-33-induced synthesis of IL-13 in mast cells. Consistent with these findings, we observed that in an IL-33-administered asthmatic airway inflammation model, IL-13 levels were markedly increased in bronchoalveolar lavage fluid, but its levels were markedly suppressed by treatment with inhibitors of 5-LO, 12-LO orBLT2, further suggesting roles of 5-/12-LO in IL-33-induced IL-13 production. Conclusion: Our results suggest that "MyD88-5-/12-LO-BLT2-NF-kappa B" cascade significantly contributes to the IL-33-induced synthesis of IL-13 in mast cells, thus potentially contributing to asthmatic development and exacerbation. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.subject | LEUKOTRIENE B-4 RECEPTOR | - |
dc.subject | AIRWAY INFLAMMATION | - |
dc.subject | ADAPTIVE IMMUNITY | - |
dc.subject | ALLERGIC-ASTHMA | - |
dc.subject | MURINE MODEL | - |
dc.subject | IL-33 | - |
dc.subject | INTERLEUKIN-33 | - |
dc.subject | MICE | - |
dc.subject | BLT2 | - |
dc.subject | RECONSTITUTION | - |
dc.title | 5-/12-Lipoxygenase-linked cascade contributes to the IL-33-induced synthesis of IL-13 in mast cells, thus promoting asthma development | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Jae-Hong | - |
dc.identifier.doi | 10.1111/all.13294 | - |
dc.identifier.scopusid | 2-s2.0-85029214937 | - |
dc.identifier.wosid | 000419871000008 | - |
dc.identifier.bibliographicCitation | ALLERGY, v.73, no.2, pp.350 - 360 | - |
dc.relation.isPartOf | ALLERGY | - |
dc.citation.title | ALLERGY | - |
dc.citation.volume | 73 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 350 | - |
dc.citation.endPage | 360 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Allergy | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Allergy | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | LEUKOTRIENE B-4 RECEPTOR | - |
dc.subject.keywordPlus | AIRWAY INFLAMMATION | - |
dc.subject.keywordPlus | ADAPTIVE IMMUNITY | - |
dc.subject.keywordPlus | ALLERGIC-ASTHMA | - |
dc.subject.keywordPlus | MURINE MODEL | - |
dc.subject.keywordPlus | IL-33 | - |
dc.subject.keywordPlus | INTERLEUKIN-33 | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | BLT2 | - |
dc.subject.keywordPlus | RECONSTITUTION | - |
dc.subject.keywordAuthor | BLT2 | - |
dc.subject.keywordAuthor | IL-13 | - |
dc.subject.keywordAuthor | IL-33 | - |
dc.subject.keywordAuthor | lipoxygenase | - |
dc.subject.keywordAuthor | mast cells | - |
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