MiR-204-3p Associates with an Increased Level of IL-6 in Familial Mediterranean Fever By Targeting the PIK3 Signaling Pathway

Tomohiro Koga¹, Kiyoshi Migita², Akihiro Yachie³, Yukitaka Ueki⁴, Kazunaga Agematsu⁵, Junya Masumoto⁶, Koh-ichiro Yoshiura⁷, Katsumi Eguchi⁸ and Atsushi Kawakami¹, ¹Unit of Advanced Preventive Medical Sciences, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ²Department of Rheumatology and Clinical Research Center, Nagasaki Medical Center, Omura, Japan, ³Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan, ⁴Rheumatic and Collagen Disease Center, Sasebo Chuo Hospital, Sasebo, Japan, ⁵Department of Infectious Immunology, Shinshu University, Graduate School of Medicine, Shinshu, Japan, ⁶Department of Pathology, Division of Analyticalpathology, Ehime University Graduate School of Medicine, Toon, Japan, ⁷Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan, ⁸Department of Rheumatology and Metabolism, Sasebo City General Hospital, Sasebo, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: IL-6, MicroRNA and familial Mediterranean fever

Session Information

Date: Sunday, November 13, 2016

Title: Miscellaneous Rheumatic and Inflammatory Diseases - Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: Familial Mediterranean fever (FMF) is caused by a number of mutations of the MEFV gene, coding for a protein named pyrin that acts as a major regulatory component of the inflammasome. Accumulating evidence has shown the association of microRNAs (miRNAs) with the development of inflammatory disorders (1). However, little is known about the precise role of miRNAs in FMF. Objective: The aim of this study was to identify a serum miRNAs profile and potential biomarkers in FMF and clarify their gene targets for understanding the pathogenesis of autoinflammatory diseases.

Methods: We performed miRNA microarray (Toray 3D-gene miRNA oligo chips) to screen miRNAs in the serum from FMF in attack and in remission. We subsequently examined the effect of candidate miRNAs on cytokine production by using THP-1 cells. Macrophages derived from THP-1 cells were transfected with miRNA mimics or miRNA inhibitor and stimulated with LPS+ATP for 24 hours. We collected the supernatants for the quantification of inflammatory cytokine production. To identify the target genes, we overexpressed its miRNA and performed Agilent expression microarray (SurePrint G3 Human GE 8x60K).

Results: We found that miR-204-3p was greatly decreased in the serum from FMF patients in attack. In vitro study, the expression of miR-204-3p was suppressed by ATP+LPS stimulation in macrophages derived from THP-1 cells. Inhibition of miR-204-3p significantly induced the production of IL-6 whereas overexpression of miR-204-3p inhibited its production. Bioinformatic analysis showed that miR-204-3p is predicted to target genes implicated in Toll like receptor pathway through regulation of PIK3 signaling.

Conclusion: These data suggest that serum miR-204-3p has a potential as a useful biomarker among patients with FMF and that miR-204-3p plays a critical role as a suppressor to regulate the production of IL-6 by targeting PIK3 signaling pathway. References:

1. Singh RP, Massachi I, Manickavel S, et al. The role of miRNA in inflammation and autoimmunity. Autoimmun Rev. 2013 Oct;12(12):1160-5. Acknowledgements: This work was supported by the Japan Agency for Medical Research and Development (No. 15657398).

Disclosure: T. Koga, None; K. Migita, None; A. Yachie, None; Y. Ueki, None; K. Agematsu, None; J. Masumoto, None; K. I. Yoshiura, None; K. Eguchi, UCB Pharma, 5; A. Kawakami, None.

To cite this abstract in AMA style:

Koga T, Migita K, Yachie A, Ueki Y, Agematsu K, Masumoto J, Yoshiura KI, Eguchi K, Kawakami A. MiR-204-3p Associates with an Increased Level of IL-6 in Familial Mediterranean Fever By Targeting the PIK3 Signaling Pathway [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/mir-204-3p-associates-with-an-increased-level-of-il-6-in-familial-mediterranean-fever-by-targeting-the-pik3-signaling-pathway/. Accessed .

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