Influences of Regulation of miR-126 on Inflammation,Th17/Treg Subpopulation Differentiation, and Lymphocyte Apoptosis through Caspase Signaling Pathway in Sepsis

Inflammation. 2020 Dec;43(6):2287-2300. doi: 10.1007/s10753-020-01298-7.

Abstract

To observe the inflammatory response, differentiation of Th17/Treg subsets and apoptosis of lymphocytes, by regulating miR-126 in lymphocytes of septic rats. After using cecal ligation and puncture to establish sepsis model, miR-126 mimic and miR-126 inhibitor were used to transfect lymphocytes of septic rats in vitro and in vivo. ELISA was used to detect TNF-α, IL-6, IL-17, and IL-10, the differentiation of Th17 and Treg was measured by flow cytometry, and apoptosis of lymphocytes was observed by fluorescence microscope; the changes of caspase signaling pathway were detected by immunofluorescence, PCR, and Western blotting. The result show that the expression of miR-126 increased in sepsis. After overexpression of miR-126, the release of TNF-α, IL-6, and IL-17 decreased; the release of IL-10 increased; T lymphocyte subsets differentiated toward Treg; caspase signaling pathway weakened; and lymphocyte of apoptosis decreased compared with sepsis group. While, after inhibition of miR-126, the release of TNF-α, IL-6, and IL-17 increased; the release of IL-10 decreased; T lymphocyte subsets differentiated toward TH17; caspase signaling pathway enhanced; and lymphocyte of apoptosis increased compared with sepsis group. Taken together, regulation of miR-126 can alter the inflammatory response, differentiation of T lymphocyte subsets, and apoptosis of lymphocytes in septic rats.

Keywords: Apoptosis; Sepsis; TH17; Treg; miR-126.

MeSH terms

  • Animals
  • Apoptosis*
  • Biomarkers / metabolism
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Caspases / metabolism*
  • Cell Differentiation
  • Gene Expression Regulation*
  • Inflammation
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • MicroRNAs / metabolism*
  • Microscopy, Fluorescence
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / metabolism*
  • Sepsis / physiopathology
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes, Regulatory / immunology
  • Th17 Cells / immunology*

Substances

  • Biomarkers
  • MIRN126 microRNA, rat
  • MicroRNAs
  • Caspase 3
  • Caspase 9
  • Caspases