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MicroRNA and interleukin 6 interplay in the adipose tissue of rheumatoid arthritis patients

1, 2, 3, 4, 5, 6

 

  1. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
  2. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
  3. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, and Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden.
  4. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.
  5. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, and Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden.
  6. Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, and Rheumatology Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden. malin.erlandsson@rheuma.gu.se

CER15249
2023 Vol.41, N°1
PI 0032, PF 0040
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PMID: 35579086 [PubMed]

Received: 15/10/2021
Accepted : 14/02/2022
In Press: 29/04/2022
Published: 23/01/2023

Abstract

OBJECTIVES:
MicroRNAs (miRs) are non-translated RNA sequences that elicit negative control over protein expression. The adipose tissue (AT) is considered the major producer of miRs and inflammatory interleukin 6 (IL-6). This study aims to investigate the relationship between production of IL-6 and miRs in AT.
METHODS:
IL-6 gene expression was analysed in RNA extracts from subcutaneous AT of 75 patients with rheumatoid arthritis (RA), with qPCR. Genome-wide profile of human miRs (2565 miRs, 96.6%) was analysed in 35 AT samples on 3D microarray. The miR-processing proteins Dicer, Drosha and DGCR8 were analysed with qPCR. In silico prediction of protein targets for the differentially expressed (DE) miRs (p<0.05; log2FC >±0.5) was conducted by DIANA software. Seven AT samples were stimulated in vitro with IL-6 or IL-6+IL-6R antibody tocilizumab and analysed for the miR processing proteins.
RESULTS:
We identified 30 DE miRs between AT with high and low IL-6 mRNA, of which 26 miRs were inversely related with IL-6 levels. DE miRs were predicted to interfere in oestrogen (p=0.001), FoxO (p=0.006) and insulin (p=0.03) signalling pathways. High expression of IL-6 in AT was associated with significantly higher expression of Dicer (p=0.04) and Drosha (p=0.04), while inhibition of IL-6 signalling with tocilizumab decreased the levels of total miRs processing enzymes (p=0.003).
CONCLUSIONS:
IL-6 mRNA production in AT has a negative effect on the miRs expression profile and it increases miR-production capacity.

DOI: https://doi.org/10.55563/clinexprheumatol/f4vlvt

Rheumatology Article