- Title
- MicroRNA-487b is a negative regulator of macrophage activation by targeting IL-33 production
- Creator
- Xiang, Yang; Eyers, Fiona; Herbert, Cristan; Tay, Hock L.; Foster, Paul S.; Yang, Ming
- Relation
- Journal of Immunology Vol. 196, Issue 8, p. 3421-3428
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.1502081
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2016
- Description
- MicroRNAs (miRNAs) are short noncoding RNAs that regulate a broad spectrum of biological processes, including immune responses. Although the contributions of miRNAs to the function of immune cells are beginning to emerge, their specific roles remain largely unknown. IL-33 plays an important role in macrophage activation for innate host defense and proinflammatory responses. In this study, we report that miR-487b can suppress the levels of mRNA and protein for IL-33 during the differentiation of bone marrow-derived macrophages (BMDMs). This results in inhibition of IL-33-induced expression of Ag-presenting and costimulatory molecules and proinflammatory mediators. A luciferase assay showed that miR-487b binds to the IL-33 39-untranslated region. We also confirmed that IL-33 directly promotes the activation of BMDMs by increasing the expression of MHC class I, MHC class II, CD80/CD86, and inducible NO synthase (iNOS) in a dose-dependent manner. Exposure of BMDMs to the TLR4 ligand, LPS, decreased miR-487b expression, increased IL-33 transcript levels, and induced the production of proinflammatory mediators (e.g., iNOS, IL-1b, IL-6, and TNF-a). Treatment with a specific inhibitor of miR-487b function also resulted in increased levels of IL-33 mRNA, which augmented LPS-induced expression of these inflammatory mediators in macrophages. Collectively, our results indicate that miR-487b plays a negative regulatory role in macrophages by controlling the levels of IL-33 transcript and protein to fine-tune innate immune host defense and proinflammatory responses of these cells. Thus, miR-487b plays an important role in the regulation of macrophage homeostasis and activation by targeting IL-33 transcripts.
- Subject
- microRNAs; immune cells; bone marrow-derived macrophages (BMDMs); macrophage homeostasis
- Identifier
- http://hdl.handle.net/1959.13/1347638
- Identifier
- uon:30084
- Identifier
- ISSN:0022-1767
- Language
- eng
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