Journal
MOLECULAR IMMUNOLOGY
Volume 117, Issue -, Pages 168-179Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2019.10.009
Keywords
Sepsis; Trauma; Mice model; RAW264.7; Inflammation; LncRNA; NEAT1; miR-495-3p/STAT3; miR-211/PI3K/AKT
Categories
Funding
- Shanghai Rising-Star Program [18QA1405400]
- National Natural Science Foundation of China [81601910, 81571887, 21502225]
- China Postdoctoral Science Foundation [2016M592936]
- Shanghai Health and Family Planning Commission Funds [201540380]
- Military Medical Research Foundation from the Secondary Military Medical University [2017JS15]
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Objective: This investigation was intended to elucidate 1ncRNA-miRNA networks that could explain inflammation underlying sepsis progression. Methods: In the first place, four kinds of mice models were established, namely, SHAM group (n = 30), trauma (TH) group (n = 30), lipopolysaccharide (LPS) group (n = 30) and TH + LPS group (n = 30). Their lung, spleen and liver tissues were gathered for determination of TNF-alpha, IL-6, IL-10 and MCP-1 levels. Furthermore, mouse mononuclear macrophage leukemia cell line (RAW264.7) was stimulated by LPS to establish inflammation cell models. Then si-NEAT1s, pcDNA3.1-NEAT1, miR-495-3p mimic, miR-495-3p inhibitor, miR-NC, miR-211 mimic and miR-211 inhibitor were, respectively, transfected into the cells, so as to observe the impacts of NEAT1, miR-495-3p and miR-211 on cytokine levels released by the cells. Results: The survival condition of mice in the TH + LPS group was undesirable, in relative to mice in the LPS group and SHAM group (both P < 0.05). High-level NEAT1 and low-level miR-495-3p/miR-211 were associated with poor survival of mice in the TH + LPS group (P < 0.05). Additionally, the correlation between NEAT1/miR-495-3p/miR-211 level and cytokine level was the strongest among TH + LPS-treated mice, in comparison to mice treated by TH or LPS. Furthermore, up-regulation of NEAT1 level and down-regulation of miR-495-3p/miR-211 level could aggravate inflammation in LPS-treated RAW264.7 cells. The miR-495-3p and miR-211 herein, were both subjected to sponging of NEAT1, possibly affected inflammation responses in RAW264.7 cells, respectively, through modulating STAT3 and PI3K/AKT signaling. Conclusion LncRNA NEAT1 exhibited great potential sepsis diagnosis and treatment, considering its modifying miR-495-3p/STAT3 axis and miR-211/PI3K/AKT axis in inflammation cell models.
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