MicroRNA-101-3p Downregulates TLR2 Expression, Leading to Reduction in Cytokine Production by Treponema pallidum-Stimulated Macrophages
| Autor: | Jieyi Yang, Heping Zheng, Fangwen Liang, Chengsong Wan, Fei Zou, Bin Yang, Liuyuan Wang, Jun Zhang, Xiaohui Zhang, Qiwei Zhang, Shuqing Mei, Zhili Rong, Wujian Ke, Tao Huang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Small interfering RNA THP-1 Cells medicine.medical_treatment Interleukin-1beta Down-Regulation Dermatology Biology Biochemistry Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system medicine Humans Syphilis Treponema pallidum Molecular Biology Toll-like receptor Treponema Interleukin-6 Tumor Necrosis Factor-alpha Macrophages Cell Biology biology.organism_classification Molecular biology Interleukin-12 Healthy Volunteers Toll-Like Receptor 2 TLR2 MicroRNAs 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Case-Control Studies Host-Pathogen Interactions Tumor necrosis factor alpha Female |
| Zdroj: | The Journal of investigative dermatology. 140(8) |
| ISSN: | 1523-1747 |
| Popis: | Treponema pallidum (Tp) infection–induced immune responses can cause tissue damage. However, the underlying mechanism by which Tp infection induces immune response is unclear. Recent studies suggest a regulatory role of microRNAs in host immunity. We assessed whether microRNAs also have a regulatory role in immune response to Tp infection in vitro. Our results showed that microRNA-101-3p (miR-101-3p) levels were significantly higher in peripheral blood mononuclear cells of patients with primary syphilis and those in the serofast state, whereas toll-like receptor (TLR) 2 levels were higher in patients with syphilis than in healthy controls. In vitro, stimulation of THP-1 cells with Tp increased miR-101-3p expression. Moreover, miR-101-3p reduced expression levels of TLR2 mRNA and protein in THP-1 cells via binding to the 3′ untranslated region of TLR2. Likewise, miR-101-3p inhibited production of inflammatory cytokines, including IL-1β, IL-6, tumor necrosis factor-α, and IL-12, in Tp-stimulated macrophages. IL-1β and IL-6 mRNA expression levels were reduced by transfection of macrophages with a TLR2-specific small interfering RNA. Conversely, overexpression of TLR2 upregulated cytokine expression. Patients with secondary syphilis exhibited the highest levels of plasma IL-6, which were negatively correlated with miR-101-3p. In conclusion, Tp infection upregulates miR-101-3p expression, which in turn inhibits the TLR2 signaling pathway, leading to reduced cytokine production. |
| Databáze: | OpenAIRE |
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