Lipopolysaccharide/TLR4 Stimulates IL-13 Production through a MyD88-BLT2-Linked Cascade in Mast Cells, Potentially Contributing to the Allergic Response
DC Field | Value | Language |
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dc.contributor.author | Lee, A-Jin | - |
dc.contributor.author | Ro, MyungJa | - |
dc.contributor.author | Cho, Kyung-Jin | - |
dc.contributor.author | Kim, Jae-Hong | - |
dc.date.accessioned | 2021-09-03T03:51:27Z | - |
dc.date.available | 2021-09-03T03:51:27Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2017-07-15 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/82817 | - |
dc.description.abstract | In an experimental asthma model, the activation of TLR4 by bacterial LPS occasionally exacerbates allergic inflammation through the production of Th2 cytokines, and mast cells have been suggested to play a central role in this response. However, the detailed mechanism underlying how LPS/TLR4 stimulates the production of Th2 cytokines, especially IL-13, remains unclear in mast cells. In the current study, we observed that the expression levels of leukotriene B4 receptor-2 (BLT2) and the synthesis of its ligands were highly upregulated in LPS-stimulated bone marrow-derived mast cells and that BLT2 blockade with small interfering RNA or a pharmacological inhibitor completely abolished IL-13 production, suggesting a mediatory role of the BLT2 ligand-BLT2 axis in LPS/TLR4 signaling to IL-13 synthesis in mast cells. Moreover, we demonstrated that MyD88 lies upstream of the BLT2 ligand-BLT2 axis and that this MyD88-BLT2 cascade leads to the generation of reactive oxygen species through NADPH oxidase 1 and the subsequent activation of NF-kappa B, thereby mediating IL-13 synthesis. Interestingly, we observed that costimulation of LPS/TLR4 and IgE/Fc epsilon RI caused greatly enhanced IL-13 synthesis in mast cells, and blockading BLT2 abolished these effects. Similarly, in vivo, the IL-13 level was markedly enhanced by LPS administration in an OVA-induced asthma model, and injecting a BLT2 antagonist beforehand clearly attenuated this increase. Together, our findings suggest that a BLT2-linked cascade plays a pivotal role in LPS/TLR4 signaling for IL-13 synthesis in mast cells, thereby potentially exacerbating allergic response. Our findings may provide insight into the mechanisms underlying how bacterial infection worsens allergic inflammation under certain conditions. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.subject | RECEPTOR 4-MEDIATED MODIFICATION | - |
dc.subject | AIRWAY INFLAMMATION | - |
dc.subject | ENDOTOXIN EXPOSURE | - |
dc.subject | INNATE IMMUNITY | - |
dc.subject | ASTHMA | - |
dc.subject | INHALATION | - |
dc.subject | CYTOKINES | - |
dc.subject | PATHWAY | - |
dc.title | Lipopolysaccharide/TLR4 Stimulates IL-13 Production through a MyD88-BLT2-Linked Cascade in Mast Cells, Potentially Contributing to the Allergic Response | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Jae-Hong | - |
dc.identifier.doi | 10.4049/jimmunol.1602062 | - |
dc.identifier.scopusid | 2-s2.0-85023178535 | - |
dc.identifier.wosid | 000405273600008 | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.199, no.2, pp.409 - 417 | - |
dc.relation.isPartOf | JOURNAL OF IMMUNOLOGY | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 199 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 409 | - |
dc.citation.endPage | 417 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Immunology | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.subject.keywordPlus | RECEPTOR 4-MEDIATED MODIFICATION | - |
dc.subject.keywordPlus | AIRWAY INFLAMMATION | - |
dc.subject.keywordPlus | ENDOTOXIN EXPOSURE | - |
dc.subject.keywordPlus | INNATE IMMUNITY | - |
dc.subject.keywordPlus | ASTHMA | - |
dc.subject.keywordPlus | INHALATION | - |
dc.subject.keywordPlus | CYTOKINES | - |
dc.subject.keywordPlus | PATHWAY | - |
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