Oncotarget

Research Papers:

MiR-146a negatively regulates dectin-1-induced inflammatory responses

Leilei Du, Xu Chen, Zhimin Duan, Caixia Liu, Rong Zeng, Qing Chen and Min Li _

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Oncotarget. 2017; 8:37355-37366. https://doi.org/10.18632/oncotarget.16958

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Abstract

Leilei Du1,*, Xu Chen1,*, Zhimin Duan1, Caixia Liu1, Rong Zeng1, Qing Chen2,*, Min Li1,*

1From Institute of Dermatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing 210042, China

2Jiangsu Province Blood Center, Nanjing, Jiangsu 210042, China

*These authors have contributed equally to this work

Correspondence to:

Min Li, email: [email protected]

Qing Chen, email: [email protected]

Keywords: MiR-146a, Candida albicans, β-glucan, dectin-1, inflammatory responses

Received: October 20, 2016     Accepted: March 29, 2017     Published: April 08, 2017

ABSTRACT

Dectin-1 is the critical sensor for β-glucan from Candida which is the most common human fungal pathogen and cause superficial and system infection. MicroRNAs (miRNAs) play crucial roles in regulating innate immunity. However, the functional role of miRNAs in inflammatory response dependent on the activation of dectin-1 pathway has not been defined. In the present study, we found insoluble β-glucan from the cell wall of Candida albicans (CaIG) was able to increase the production of of IL-6 and TNFα through Dectin-1-Syk-NF-κB and p38MAPK pathway. MiRNAs profiles combined with real-time PCR validation revealed that miR-146a, miR-30-5p, miR-210-3p expression level were increased in THP-1 cells treated with CaIG. The interaction between Dectin-1 and CaIG resulted in an long lasting increase of miR-146a expression dependent on Dectin-1-Syk-NF-κB, p38MAPK, contrasting with a rapid and transient increase of IL-6 and TNFα. Overexpression of miR-146a significantly suppressed the production of IL-6 and TNFα. MiR-146a mimics inhibited CaIG-induced activity of p-IκBα and translocation of NF-κB p65. Luciferase reporter assays showed miR-146a inhibited NF-κB promoter-binding activity. Together, our data suggest miR-146a may play the potent negative feedback regulator in inflammatory response following Dectin-1 stimulation.


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