Critical Care: Mechanisms of Infections |

The Mechanism of miRNSAs on Regulating Lymphocyte Proliferation and Apoptosis in Sepsis FREE TO VIEW

Dan Liu; Lixin Xie
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Chinese PLA General Hospital, Beijing, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A180. doi:10.1016/j.chest.2016.02.186
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SESSION TITLE: Mechanisms of Infections

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, April 17, 2016 at 04:00 PM - 05:00 PM

PURPOSE: We discuss the potential role of miR-223, miR-15a, miR-16 in regularing the proliferation and apoptosis of lymphocyte in sepsis and aim to find new targets for sepsis treatment.

METHODS: Real time quantitative PCR (Real Time-PCR, RT-PCR)/Western blot/MTT cell proliferation and toxicity assay/Flow cytometry

RESULTS: 1) The level of miR-15a/16 was statistical difference between survival group non-survival group in the 1, 7, 10 and 15 days. White blood cells were sorted into monocytes, lymphocytes and neutrophils and miR-223 was significantly high in lymphocyte. 2) The expression of miR-223/15a/16 was positively correlated with lymphocytes and lymphocyte apoptosis. Cell number ratio of G1 phase and S phase reduced significantly in Agomir 223 group compared to Antagomir 223 group, indicating miR-223 causes cell cycle arrest. 3) We cultured whole blood of septic patients and transfected with Antagomir-223 and Antagomir NC. The early apoptosis proportion of lymphocyte was significantly lower in Antagomir-223 group than control. 4) FAS stimulating antibody was used to induce apoptosis. Result of MTT tests showed that the OD value of agomir 15a/16 groups are significantly lower than control, the OD value of antagomir 15a/16 groups are significantly higher than control. miR-15a/16 were proved to inhibit cell proliferation. Flow cytometry showed the proportion of apoptosis in agomir 15a/16 groups are significantly higher than the control. 5) Western blot showed phosphorylation FOXO1 was decreased in Agomir 15a/16 groups and increased in antagomir 15A/16 groups, indicating miR-15a/16 increases the non-phosphorylation form of FOXO1, which actives FOXO1 and its downstream apoptosis-related molecules.

CONCLUSIONS: 1. We found that the expression of miR-223 was significantly high in sepsis group (158 patients) compare to health control. The expression of miR-223 was positively correlated with lymphocytes and lymphocyte apoptosis. miR-15a/16 could assess the severity of sepsis, its dynamic change predict the patients’ prognosis. 2. MiR-223/15a/16 can promote FAS-mediated apoptosis in Jurkat T cells and inhibit of cell proliferation. 3. MiR-15a/16 could increase the non-phosphorylation form of FOXO1 and active FOXO1, specific mechanisms still need further study.

CLINICAL IMPLICATIONS: The present research further study the regulatory mechanism of those miRNAs in lymphocyte in sepsis. We also provide a new target to treat sepsis.

DISCLOSURE: The following authors have nothing to disclose: Dan Liu, Lixin Xie

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