Respiratory Disorder at the End of Surgery for Peritonitis Due to Colorectal Perforation Is a Critical Predictor of Postoperative Sepsis

Mouri, Takashi; Kawahara, Hidejiro; Matsumoto, Tomo; Ishida, Katsuhiro; Misawa, Takeyuki; Yanaga, Katsuhiko

doi:10.21873/invivo.11607

Cited by 2 publications

(2 citation statements)

References 14 publications

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“…Sepsis, resulting from complicated infection, trauma, shock, and major surgery, can lead to circulatory disturbance and multiple organ dysfunction [ 1 – 3 ]. As a major cause of in-hospital death in intensive care units worldwide [ 4 – 6 ], sepsis might eventually deteriorate in a vicious cycle of uncontrolled inflammatory reactions and an immunosuppressive state [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Sestrin2 protects dendrite cells against ferroptosis induced by sepsis

Ren

Wang

et al. 2021

Cell Death Dis

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Ferroptosis is a nonapoptotic form of programmed cell death triggered by the accumulation of reactive oxygen species (ROS) depended on iron overload. Although most investigations focus on the relationship between ferroptosis and cancer, neurodegenerative diseases, and ischemia/reperfusion injury, research on ferroptosis induced by immune-related inflammatory diseases, especially sepsis, is scarce. Sestrin2 (Sesn2), a highly evolutionary and stress-responsive protein, is critically involved in defense against oxidative stress challenges. Upregulated expression of Sesn2 has been observed in preliminary experiments to have an antioxidative function in the context of an inflammatory response. Nevertheless, the underlying function of Sesn2 in inflammation-mediated ferroptosis in the immune system remains uncertain. The current study aimed to demonstrate the protective effect of Sesn2 on ferroptosis and even correlations with ferroptosis and the functions of ferroptotic-dendritic cells (DCs) stimulated with lipopolysaccharide (LPS). The mechanism underlying DCs protection from LPS-induced ferroptosis by Sesn2 was further explored in this study. We found that the immune response of DCs assessed by co-stimulatory phenotypes was gradually enhanced at the peak time of 12 h upon 1 μg/ml LPS stimulation while ferroptosis in DCs treated with LPS at 24 h was significantly detected. LPS-induced ferroptosis showed a suppressive impact on DCs in phenotypic maturation, which was conversely relieved by the ferroptotic inhibitor. Compared with wild-type (WT) mice, DCs in genetic defective mice of Sesn2 (Sesn2−/−) exhibited exacerbated ferroptosis. Furthermore, the protective effect of Sesn2 on ferroptosis was noticed to be associated with the ATF4-CHOP-CHAC1 pathway, eventually exacerbating ferroptosis by degrading of glutathione. These results indicate that Sesn2 can suppress the ferroptosis of DCs in sepsis by downregulating the ATF4-CHOP-CHAC1 signaling pathway, and it might play an antioxidative role.

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Section: Introductionmentioning

confidence: 99%

Sestrin2 protects dendrite cells against ferroptosis induced by sepsis

Ren

Wang

et al. 2021

Cell Death Dis

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“…Sepsis is still a nagging medical syndrome that occurs when a serious infection exceeds the host’s scavenging ability and leads to systemic inflammatory response syndrome. Sepsis is a common complication derived from complicated infection, trauma, shock, and major surgery [ 1 – 3 ]. As a heavy burden on national health and the economy, sepsis is a leading cause of hospital death in intensive care units (ICUs) worldwide [ 4 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

TNF-α-induced protein 8-like 2 negatively regulates the immune function of dendritic cells by suppressing autophagy via the TAK1/JNK pathway in septic mice

Liu

Ren

et al. 2021

Cell Death Dis

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Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TIPE2) is a newly discovered negative immunoregulatory protein that is involved in various cellular immune responses to infections. However, the underlying mechanism by which TIPE2 affects the immune function of dendritic cells (DCs) is not yet understood. This study aimed to determine the correlations among DCs TIPE2 expression, autophagic activity and immune function in the context of sepsis. In addition, the signaling pathway by which TIPE2 regulates autophagy in DCs was investigated. We reported for the first time that TIPE2 overexpression (knock-in, KI) exerted an inhibitory effect on autophagy in DCs and markedly suppressed the immune function of DCs upon septic challenge both in vitro and in vivo. In addition, TIPE2 knockout (KO) in DCs significantly enhanced autophagy and improved the immune response of DCs in sepsis. Of note, we found that the transforming growth factor-β (TGF-β)-activated kinase-1 (TAK1)/c-Jun N-terminal kinase (JNK) pathway was inhibited by TIPE2 in DCs, resulting in downregulated autophagic activity. Collectively, these results suggest that TIPE2 can suppress the autophagic activity of DCs by inhibiting the TAK1/JNK signaling pathway and further negatively regulate the immune function of DCs in the development of septic complications.

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Respiratory Disorder at the End of Surgery for Peritonitis Due to Colorectal Perforation Is a Critical Predictor of Postoperative Sepsis

Cited by 2 publications

References 14 publications

Sestrin2 protects dendrite cells against ferroptosis induced by sepsis

Sestrin2 protects dendrite cells against ferroptosis induced by sepsis

TNF-α-induced protein 8-like 2 negatively regulates the immune function of dendritic cells by suppressing autophagy via the TAK1/JNK pathway in septic mice

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