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Abstract Number: 2436

MiR-146a Upregulates the TLR4/NF-κb Signaling Pathway to Promote Cytokine Expression and Synovial Fibroblast Proliferation in Rheumatoid Arthritis

Yuan-hao Wu1,2, Wei Liu1, Lei Zhang3, Bin Xue3, Yi Wang3, Xiao-ya Liu3, Yang Ji4, Ran Duan3, Yue Cai3 and Bo Zhang3, 1Department of Rheumatology and Immunology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China, 2Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China, 3First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China, 4The 272nd Hospital of Chinese People's Liberation Army, Tianjin, China

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Cell Signaling, MicroRNA, NFB, rheumatoid arthritis, synovium and toll-like receptors

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Session Information

Date: Tuesday, November 7, 2017

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: To investigate the role of miR-146a in the activation of toll-like receptor-4 (TLR4)/ nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, and the effect of miR-146a in cytokines expression and synoviocytes proliferation during rheumatoid arthritis (RA).

Methods: Synovial tissues were collected from RA patients who received arthroscopic synovectomy in the Department of Rheumatism at our hospital. Cells were categorized into a blank control group, a negative control group, a miR-146a mimics group and a miR-146a inhibitors group. The cholecystokinin (CCK)-8 assay was used to measure the inhibition on cell proliferation rate. TLR4 mRNA level, as well as the mRNA expressions of NF-κB, interleukin (IL)-1β, IL-6, IL-8, IL-17, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-3, Seprase, and inducible nitric oxide synthase (iNOS) were detected by the reverse transcription-polymerase chain reaction (RT-PCR). Western blot was used to measure TLR4 and NF-κB proteins, and the expressions of IL-1β, IL-6, IL-8, IL-17, Seprase, MMP-3 and prostaglandin E2 (PGE2) were measured by enzyme linked immunosorbent assay (ELISA). The content of nitric oxide (NO) was measured by the Griess method.

Results: The CD3 and CD14 expression rate gradually decreased, and the CD90 expression rate gradually increased. After the third generation of cell culture, the CD90 expression rate (96.48%) was significantly higher than those of CD3 (1.17%) and CD14 (1.27%). After culturing for 48h and 72h, cell proliferation in the miR-146a mimics group was significantly increased (both P < 0.05) as compared with the blank group, while that in the miR-146a inhibitors group significantly reduced (both P < 0.05). With an extended time of cell culture, the change in cell proliferation was more significant, and differences were observed at each time point (all P < 0.05). Compared with the blank group, the expressions of TLR4, NF-κB, IL-1, IL-6, IL-8, IL-17, COX-2, MMP-3, Seprase, iNOS and NO content in the miR-146a mimics group increased significantly (all P < 0.05), but in the miR-146a inhibitors group, these values significantly reduced (all P < 0.05).

Conclusion: The inhibition of miR-146a expression could block the TLR4/NF-κB signaling pathway, and inhibited synovial fibroblast proliferation and cytokine expressions in RA.


Disclosure: Y. H. Wu, None; W. Liu, None; L. Zhang, None; B. Xue, None; Y. Wang, None; X. Y. Liu, None; Y. Ji, None; R. Duan, None; Y. Cai, None; B. Zhang, None.

To cite this abstract in AMA style:

Wu YH, Liu W, Zhang L, Xue B, Wang Y, Liu XY, Ji Y, Duan R, Cai Y, Zhang B. MiR-146a Upregulates the TLR4/NF-κb Signaling Pathway to Promote Cytokine Expression and Synovial Fibroblast Proliferation in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mir-146a-upregulates-the-tlr4nf-%ce%bab-signaling-pathway-to-promote-cytokine-expression-and-synovial-fibroblast-proliferation-in-rheumatoid-arthritis/. Accessed .
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mir-146a-upregulates-the-tlr4nf-%ce%bab-signaling-pathway-to-promote-cytokine-expression-and-synovial-fibroblast-proliferation-in-rheumatoid-arthritis/

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