scholarly journals Role of the transcription factor STAT3 in the development of multiple organ injury in mice with cecal ligation and puncture-induced sepsis

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO4-3-33
Author(s):  
Kengo Tomita ◽  
Samar Imbaby ◽  
Takuya Sakamoto ◽  
Yuichi Hattori
Keyword(s):  
Transcription Factor ◽  
Cecal Ligation ◽  
Multiple Organ ◽  
Organ Injury ◽  
Cecal Ligation And Puncture ◽  
Multiple Organ Injury

Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression

2021 ◽  
pp. 153537022110156
Author(s):  
Zhixia Chen ◽  
Yihui Chen ◽  
Xianwei Jin ◽  
Ying Liu ◽  
Zhenzhen Shao ◽  
...  
Keyword(s):  
Sham Group ◽  
Cecal Ligation ◽  
Lavage Fluid ◽  
Peritoneal Macrophages ◽  
Multiple Organ ◽  
Organ Injury ◽  
Cecal Ligation And Puncture ◽  
Erk Activation ◽  
Tnf Α ◽  
Multiple Organ Injury

Sepsis is characterized by persistent systemic inflammation, which can cause multi-organ dysfunction. The poly polymerase-1 inhibitor olaparib possesses anti-inflammatory properties. This study aimed to assess the effects of olaparib (pre- and post-treatments) on sepsis, and to investigate whether it could suppress CD14 expression via the ERK pathway in polymicrobial sepsis and peritoneal macrophages models. Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Fifty mice were randomly divided into five groups: The sham group was treated with vehicle or olaparib, the cecal ligation and puncture group with vehicle or with olaparib (5 mg/kg i.p.) 1 h before or 2 h after surgery. Olaparib pretreatment significantly improved the survival of septic mice ( P <  0.001). Pre- and post-treatment of mice with olaparib partly alleviated cecal ligation and puncture-induced organ injury by decreasing the amounts of the pro-inflammatory mediators TNF-α and IL-6 as well as bacterial burden in the serum, peritoneal lavage fluid, and organs ( P <  0.05). The protective effect of olaparib was associated with CD14 suppression via inhibition of ERK activation. Olaparib facilitated negative regulation of ERK-mediated CD14 expression, which may contribute to multi-organ injury in sepsis.

Interleukin-10 Gene Transfer: Prevention of Multiple Organ Injury in a Murine Cecal Ligation and Puncture Model of Sepsis

2006 ◽  
Vol 31 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Burhan Kabay ◽  
Cetin Kocaefe ◽  
Atac Baykal ◽  
Hilmi Özden ◽  
Cengiz Baycu ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cecal Ligation ◽  
Interleukin 10 ◽  
Multiple Organ ◽  
Organ Injury ◽  
Cecal Ligation And Puncture ◽  
Puncture Model ◽  
Multiple Organ Injury

scholarly journals Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

2022 ◽  
Vol 9 ◽  
Author(s):  
Zhengru Liu ◽  
Mingming Qi ◽  
Shan Tian ◽  
Qian Yang ◽  
Jian Liu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Tight Junctions ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pancreatic Acinar Cells ◽  
Stat3 Pathway ◽  
Specific Protease ◽  
Ubiquitin Specific Protease ◽  
Multiple Organ Injury

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.

The Role of Tumor Necrosis Factor-α (TNF) in Multiple Organ Injury

CHEST Journal ◽  
1989 ◽  
Vol 95 (3) ◽  
pp. 233S-234S
Author(s):  
Robert M. Strieter ◽  
Daniel G. Remick ◽  
Joseph P. Lynch ◽  
Steven L. Kunkel
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Multiple Organ ◽  
Organ Injury ◽  
Factor Α ◽  
Multiple Organ Injury ◽  
Necrosis Factor

scholarly journals The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Sun ◽  
Jin Tan ◽  
Yuyang Miao ◽  
Qiang Zhang
Keyword(s):  
Immune Regulation ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Immune Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Cellular Expression ◽  
Obstructive Sleep ◽  
Multiple Organ Injury

AbstractHypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea.

scholarly journals Double-Stranded RNA Dependent Kinase R Regulates Antibacterial Immunity in Sepsis

2020 ◽  
pp. 1-12
Author(s):  
Yanliang Yang ◽  
Lingli Xie ◽  
Yanjun Zhong ◽  
Xiaoli Zhong ◽  
Ran Meng ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Critical Role ◽  
Cecal Ligation ◽  
Organ Injury ◽  
Cecal Ligation And Puncture ◽  
Bacterial Sepsis ◽  
Double Stranded Rna ◽  
Important Regulator ◽  
Genetic Deletion

Double-stranded RNA dependent kinase R (PKR) is originally identified as an intracellular sensor of viral infection, but its role in bacterial infection remains largely unknown. Here we report that PKR was an important regulator of antibacterial immunity in sepsis. Genetic deletion of PKR or pharmacological inhibition of its kinase activity markedly increased bacterial loads, organ injury, and mortality in polymicrobial infection induced by cecal ligation and puncture (CLP). In contrast, PKR deficiency or inhibition did not affect bacterial loads, organ injury, or mortality when mice were systemically challenged with <i>Escherichia coli</i>, an abundant microbe in the gastrointestinal tract. PKR deficiency or inhibition markedly decreased the release of interleukin (IL)-1β after CLP. Defect in IL-1 signaling phenocopied PKR deficiency or inhibition in CLP-induced bacterial sepsis. Taken together, these findings identified a critical role of the PKR signaling pathway in antibacterial immunity.

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