Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus Feifei Zhang a, b, 1 , Lingling Wu a, 1 , Jie Qian a, 1 , Bo Qu a , Shiwei Xia a , Ting La b , Yanfang Wu a , Jianyang Ma a , Jing Zeng a , Qiang Guo a , Yong Cui d , Wanling Yang e , Jiaqi Huang f , Wei Zhu f , Yihong Yao f , Nan Shen a, b, c, * , Yuanjia Tang a, b, ** a Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China b Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China c The Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA d Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, China e Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China f Cellular Biomedicine Group Inc., Shanghai, China article info Article history: Received 23 January 2016 Received in revised form 18 July 2016 Accepted 25 July 2016 Available online 29 July 2016 Keywords: Long noncoding RNA NEAT1 TLR4 Systemic lupus erythematosus Cytokines abstract Long noncoding RNAs (lncRNAs) have recently been identified to be tightly linked to diverse human diseases. However, our knowledge of Systemic Lupus Erythematosus (SLE)-related lncRNAs remains limited. In the present study we investigated the contribution of the lncRNA NEAT1 to the pathogenesis of SLE. Here, we found NEAT1 expression was abnormally increased in SLE patients and predominantly expressed in human monocytes. Additionally, NEAT1 expression was induced by LPS via p38 activation. Silencing NEAT1 significantly reduced the expression of a group of chemokines and cytokines, including IL-6, CXCL10, etc., which were induced by LPS continuously and in late stages. Furthermore, it was identified the involvement of NEAT1 in TLR4-mediated inflammatory process was through affecting the activation of the late MAPK signaling pathway. Importantly, there was a positive correlation between NEAT1 and clinical disease activity in SLE patients. In conclusion, the increased NEAT1 expression may be a potential contributor to the elevated production of a number of cytokines and chemokines in SLE patients. Our findings suggest lncRNA contributes to the pathogenesis of lupus and provides potentially novel target for therapeutic intervention. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Systemic Lupus Erythematosus (SLE) is a chronic, multi-system autoimmune disease [1,2]. Though lots of work has been done to elucidate the pathogenesis of SLE, the exact etiology of SLE is still unknown. Conventionally, SLE is characterized as a disease pri- marily caused by autoantibody production and immune complex deposition. However, emerging evidence suggests the innate im- mune response is also crucial contributor to the pathogenesis of SLE [3e5]. Monocytes were a crucial component of innate immune. Acti- vation of monocytes results in the up-regulation of several surface molecules and the secretion of multiple monokines which partici- pate in various functions such as chemotaxis (eg, CCR2, MCP-1), adhesion (eg, ICAM-I), phagocytosis, antigen presentation and co- stimulation, modulation of lymphocyte effector functions, and differentiation to macrophages and dendritic cells (DCs) [6]. Evi- dences showed that monocytes severely altered in phenotype and lineage flexibility in SLE patients which indicated disturbances in the monocytes initiating the auto-reactive cascade in SLE [7]. * Corresponding author. Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Shan Dong Rd (Central), Shanghai, China. ** Corresponding author. Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Shan Dong Rd (Central), Shanghai, China. E-mail addresses: nanshensibs@gmail.com (N. Shen), tangyuanjia028@163.com (Y. Tang). 1 These authors contributed equally to this work. Contents lists available at ScienceDirect Journal of Autoimmunity journal homepage: www.elsevier.com/locate/jautimm http://dx.doi.org/10.1016/j.jaut.2016.07.012 0896-8411/© 2016 Elsevier Ltd. All rights reserved. Journal of Autoimmunity 75 (2016) 96e104