The Critical Roles and Mechanisms of Immune Cell Death in Sepsis

Cheng, Zhaojun; Abrams, Simon T.; Toh, Julien; Wang, Susan Siyu; Wang, Zhi; Qian, Yu; Yu, Wenbin; Toh, Cheng‐Hock; Wang, Guozheng

doi:10.3389/fimmu.2020.01918

Cited by 68 publications

(61 citation statements)

References 160 publications

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“…At present, the uncontrolled inflammatory response is considered to be the basis for the pathogenesis of sepsis. The release of inflammatory factors in the early stage of sepsis leads to amplification of an inflammatory cascade and tissue and organ damage (20)(21)(22)(23). TNF-α and IL-6 are associated with occurrence and progress of inflammatory reactions in sepsis (24).…”

Section: Discussionmentioning

confidence: 99%

Association between miR‑126, miR‑21, inflammatory factors and T lymphocyte apoptosis in septic rats

Zou

Yang

et al. 2021

Mol Clin Oncol

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MicroRNAs (miRs) serve an important role in regulating expression levels of inflammatory factors but the underlying mechanism is still unclear. The present study aimed to observe miR-126 and miR-21 expression and apoptosis in T lymphocytes and to analyze their association with cytokine release in septic rats. The septic model rats were given intraperitoneal lipopolysaccharide (LPS) and divided into 0, 12, 24, 48 and 72 h groups. Peripheral blood was collected from each group to isolate T lymphocytes. The expression levels of miR-126 and miR-21 in T lymphocytes were observed, as well as cytokine release and apoptosis. Finally, the association between miR-126, miR-21, cytokines and apoptosis in T lymphocytes was analyzed. The release of TNF-α and IL-6 in septic rats was initially elevated but then decreased. miR-126 and miR-21 levels in T lymphocytes in septic rats were lower than those of NC rats. miR-126 and miR-21 initially decreased and then increased, whereas of apoptosis of T lymphocytes increased and then decreased, in septic rats. The expression of miR-126 was positively correlated with that of miR-21 (r= 0.316; P= 0.029) and negatively correlated with that of TNF-α (r=-0.480; P=0.001) and IL-6 (r=-0.626; P<0.001), as well as the apoptotic rate of T lymphocytes (r=-0.377; P=0.008). Furthermore, expression levels of miR-126 were negatively corrlated with caspase-3 expression levels (r=-0.606; P<0.001) and activity (r=-0.541; P<0.001). There was a negative correlation between miR-21 and levels of TNF-α (r=-0.311; P=0.032) and IL-6 (r=-0.439; P=0.002), as well as caspase-3 expression (r=-0.398; P=0.005) and activity (r=-0.378; P=0.008). However, there miR-126 expression was not correlated with apoptotic rate of T lymphocytes. Altered expression levels of miR-126 and miR-21 reflected the severity of inflammatory response and indicated levels of T lymphocyte apoptosis in septic rats.

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Section: Discussionmentioning

confidence: 99%

Association between miR‑126, miR‑21, inflammatory factors and T lymphocyte apoptosis in septic rats

Zou

Yang

et al. 2021

Mol Clin Oncol

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“…Intraperitoneal injection of HMGB1 did not show such effect [45]. Regarding the inflammatory reaction, HMGB1 mediates endotoxin shock [46], and can cause multiple organ dysfunction syndrome (MODS) [47]. It is "a late mediator of sepsis" with postponed release in comparison with "early mediators of sepsis" represented, e.g., by TNF-α [48].…”

Section: Discussionmentioning

confidence: 99%

High Mobility Group Box 1 in Pig Amniotic Membrane Experimentally Infected with E. coli O55

Šplı́chal

Šplı́chalová

2021

Biomolecules

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Intra-amniotic infections (IAI) are one of the reasons for preterm birth. High mobility group box 1 (HMGB1) is a nuclear protein with various physiological functions, including tissue healing. Its excessive extracellular release potentiates inflammatory reaction and can revert its action from beneficial to detrimental. We infected the amniotic fluid of a pig on the 80th day of gestation with 1 × 104 colony forming units (CFUs) of E. coli O55 for 10 h, and evaluated the appearance of HMGB1, receptor for glycation endproducts (RAGE), and Toll-like receptor (TLR) 4 in the amniotic membrane and fluid. Sham-infected amniotic fluid served as a control. The expression and release of HMGB1 were evaluated by Real-Time PCR, immunofluorescence, immunohistochemistry, and ELISA. The infection downregulated HMGB1 mRNA expression in the amniotic membrane, changed the distribution of HMGB1 protein in the amniotic membrane, and increased its level in amniotic fluid. All RAGE mRNA, protein expression in the amniotic membrane, and soluble RAGE level in the amniotic fluid were downregulated. TLR4 mRNA and protein expression and soluble TLR4 were all upregulated. HMGB1 is a potential target for therapy to suppress the exaggerated inflammatory response. This controlled expression and release can, in some cases, prevent the preterm birth of vulnerable infants. Studies on suitable animal models can contribute to the development of appropriate therapy.

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“…With the increasing use of antibiotics and various anti-in ammatory factors in recent years, most patients will survive the systemic acute in ammatory reaction period, but subsequently enter a longer-lasting immune dysfunction state [22]. Studies have found that the key cause of immune dysfunction in patients with sepsis is the death of lymphocytes, especially T and B lymphocyte apoptosis, is a major factor in immune dysfunction [23]. CD4+ can help B lymphocytes produce antibodies and induce T lymphocytes to transform into effector cells, and is a surface marker of Ti/Th.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

et al. 2021

Preprint

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In recent years, researchers have turned their attention to the study of the mechanism of sepsis-induced immuneparalysis, but there is still a lack of appropriate animal models that reflect the process of sepsis-induced immuneparalysis. The purpose of this study was to explore and evaluate whether a "two-hit" model of sepsis can be used as an appropriate animal model to study the mechanism of sepsis-induced immunoparalysis. Firstly, we established a sepsis model in C57BL/6J mice via cecal ligation and puncture(CLP). Routine blood tests, serum ALT and PCT, etc. were analyzed to evaluate the establishment of a CLP sepsis model on day 1 post-CLP. Secondly, the surviving mice were treated with 40µL suspension of P.aeruginosa (Pa) under anesthetic on day 4 post-CLP to establish a "two-hit" model. Gross lung specimens, and pathological examination of the lung tissue, etc. were used to evaluate whether the "two-hit" model was successfully established on days 5 and 11 post-CLP. Finally, the level of serum TNF-α and IL-6, pathological examination of the spleen and the CD4+/CD8 + ratio in blood were detected to evaluate the immune status of the model mice. The above test results proved that the "two-hit" sepsis mouse model was successfully constructed. TNF-α, IL-6, pathological examination of the spleen and the CD4+/CD8 + ratio in blood confirmed that the model was in a state of immunoparalysis. We conclude that this "two-hit" sepsis mouse model is an appropriate animal model, which can successfully replicate the pathophysiological process of in clinical patients with sepsis-induced immunoparalysis.

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The Critical Roles and Mechanisms of Immune Cell Death in Sepsis

Cited by 68 publications

References 160 publications

Association between miR‑126, miR‑21, inflammatory factors and T lymphocyte apoptosis in septic rats

Association between miR‑126, miR‑21, inflammatory factors and T lymphocyte apoptosis in septic rats

High Mobility Group Box 1 in Pig Amniotic Membrane Experimentally Infected with E. coli O55

Establishment and Evaluation of a "Two-Hit" Mouse Model of Sepsis

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