The protective role of miR-223 in sepsis-induced mortality

Abstract

Lymphocyte apoptosis appears to play an important role in immunodysfunction in sepsis. We investigated the role of miR-223 in cell proliferation and apoptosis to identify potential target downstream proteins in sepsis. We recruited 143 patients with sepsis and 44 healthy controls from the Chinese PLA General Hospital. Flow cytometry was used to sort monocytes, lymphocytes, and neutrophils from fresh peripheral blood. A miR-223 mimic and inhibitor were used for transient transfection of Jurkat T cells. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to assess expression of the miRNAs in cells. Western blot analysis was performed to measure protein expression. We evaluated the cell cycle and apoptosis by using flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Expression of miR-223 was significantly higher in the survivor group than in the nonsurvivor group. Multiple linear regression analysis revealed that SOFA scores correlated negatively with miR-223 and monocyte counts, with β coefficients (95% CI) of − 0.048 (− 0.077, − 0.019) and − 47.707 (− 83.871, − 11.543), respectively. miR-223 expression also correlated negatively with the percentage of apoptosis in lymphocytes. The rate of apoptosis in the miR-223 mimic group was significantly lower than that of the negative control, with an adverse outcome observed in the miR-223 inhibitor group. We also found that miR-223 enhanced the proliferation of Jurkat T cells and that inhibiting miR-223 had an inhibitory effect on the G1/S transition. We conclude that miR-223 can serve as a protective factor in sepsis by reducing apoptosis and enhancing cell proliferation in lymphocytes by interacting with FOXO1. Potential downstream molecules are HSP60, HSP70, and HTRA.

lncRNA OIP5‐AS1 knockdown or miR‐223 overexpression can alleviate LPS‐induced ALI/ARDS by interfering with miR‐223/NLRP3‐mediated pyroptosis

“…miR‐223 has been shown to promote the apoptosis of various cell types, such as HepG2 cells, mast cells and cardiomyocytes 26–28 . On the other hand, miR‐223 also could inhibit apoptosis and promote the proliferation of lymphocytes and keratinocytes 29,30 . The dual role of miR‐223 in cell apoptosis may be a result of miR‐223 target different genes in different cell types.…”

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review

“…They reported that miR-223 was downregulated after severe CLP surgery, with an increase of inflammatory response and myocardial depression. Some clinical studies supported these findings, showing a reduction of serum miR-223 in patients who died of sepsis [ 33 , 34 ]. It is noteworthy that a decrease in seric level of miR-223 was also linked with cardiac mortality in chronic kidney disease patients [ 35 ].…”

IL-6/STAT3 Signaling Promotes Cardiac Dysfunction by Upregulating FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes Formation in Sepsis Mice

“…One of characteristics for early sepsis is the excessive inflammation syndrome called “cytokine storm” ( 26 ). IL-6 is one of the most commonly used biomarkers of sepsis, and the level of IL-6 is positively correlated with sepsis-associated organ dysfunction and death ( 8 , 27 ).…”