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MicroRNAs as New Players in Endocrinology

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Front. Endocrinol. | doi: 10.3389/fendo.2018.00041

Two distinct interferon-γ in the orange-spotted grouper (Epinephelus coioides): molecular cloning, functional characterization, and regulation in TLR pathway by induction of miR-146a

 Wan Peng1, 2, 3, Yan Sun1, Gaofei Li1, Ruozhu Li1, Yaosi Liang1, Xu Ding1, Yong Zhang1,  Haoran Lin1 and  Danqi Lu1*
  • 1State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, College of Life Sciences, Sun Yat-sen University, China
  • 2State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center (SYSUCC), China
  • 3Department of Experimental Research, Sun Yat-sen University Cancer Center (SYSUCC), China

Interferon gamma (IFNγ) is a Th1 cytokine that is critical for innate and adaptive immunity. Toll-like receptors (TLRs) signalling pathways are critical in early host defence against invading pathogens. miR-146a has been reported to participate in the regulation of host immunity. The known mechanisms of integrations between the IFNγ and TLR signalling pathways are incompletely understood, especially in teleosts. In this study, orange-spotted grouper (Epinephelus coioides) IFNγ1 and IFNγ2, their biological activities, especially their involvements in TLR pathway were explored. We identified and cloned two IFNγ genes of E. coioides, namely EcIFNγ1 and EcIFNγ2. The produced recombinant E. coioides IFNγ1 (rEcIFNγ1) and IFNγ2 (rEcIFNγ2) proteins showed functions which are similar to those of other bony fishes, such as enhancing nitric oxide responses and respiratory burst response. rEcIFNγ2 could regulate TLR pathway by enhancing the promoter activity of miR-146a upstream sequence and thus increasing the expression level of miR-146a, which possibly targets TRAF6, a key adapter molecule in TLR signaling pathway. Taken together, these findings unravel a novel regulatory mechanism of anti-inflammatory response by IFNγ2, which could mediate TLR pathway through IFNγ2-miR-146a-TRAF6 negative regulation loop. It is suggested that IFNγ2 may provide a promising therapeutic, which may help to fine-tune the immune response.

Keywords: Epinephelus coioides, IFNγ1, IFNγ2, mir-146a, TRAF6

Received: 02 Oct 2017; Accepted: 31 Jan 2018.

Edited by:

Yan-ling Wang, Institute of Zoology (CAS), China

Reviewed by:

Tsubasa Sakai, Suntory Foundation for Life Sciences, Japan
Takashi Yazawa, Asahikawa Medical College, Japan  

Copyright: © 2018 Peng, Sun, Li, Li, Liang, Ding, Zhang, Lin and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Danqi Lu, Sun Yat-sen University, State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, College of Life Sciences, Guangzhou, China, ludanqi@mail.sysu.edu.cn