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Lipopolysaccharide/TLR4 Stimulates IL-13 Production through a MyD88-BLT2–Linked Cascade in Mast Cells, Potentially Contributing to the Allergic Response
| Content Provider | Scilit |
|---|---|
| Author | Lee, A-Jin Ro, Myungja Cho, Kyung-Jin Kim, Jae-Hong |
| Copyright Year | 2017 |
| Description | 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-κB, thereby mediating IL-13 synthesis. Interestingly, we observed that costimulation of LPS/TLR4 and IgE/FcεRI 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. |
| Ending Page | 417 |
| Page Count | 9 |
| Starting Page | 409 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1602062 |
| Alternate Webpage(s) | https://www.jimmunol.org/content/jimmunol/199/2/409.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 2 |
| Volume Number | 199 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2017-07-15 |
| Access Restriction | Open |
| Subject Keyword | Small Interfering Rna Bone Marrow Mast Cells Asthma Model Lps/tlr4 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
