Endotoxin Tolerance Attenuates Liver Ischemia/Reperfusion Injury by Down-Regulation of Interleukin-1 Receptor-Associated Kinase 4 in Kupffer Cells

Li, J.; Lai, Xiaorong; Chen, Y.; Niu, Ben; Gong, Jianping

doi:10.1016/j.transproceed.2011.05.045

Cited by 15 publications

(11 citation statements)

References 18 publications

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“…While endotoxin tolerance has been associated with protection against tissue injury and even mortality in several different disease models, [21][22][23][24][25] the immunosuppressed state of endotoxin tolerance can lead to high risk of secondary infections in certain clinical scenarios, such as septic shock. 63 We speculate that endotoxin tolerance in the placenta during pregnancy serves to blunt the inflammatory response to subsequent infectious exposures which could lead to pre-term birth and adverse neonatal outcomes and that failure of mechanisms leading to endotoxin tolerance in a subset of pregnant women may cause an exaggerated inflammatory response and pre-term labor.…”

Section: Discussionmentioning

confidence: 99%

“…19 Endotoxin tolerance is a well-described phenomenon in which organisms or cells exposed to a dose of LPS become less responsive to subsequent exposures, with decreased expression of pro-inflammatory cytokines and increased expression of anti-inflammatory cytokines. [21][22][23][24][25] During pregnancy, the maternal-fetal interface must provide a unique balance between immunosuppression in order to maintain the pregnancy and prevent rejection of the fetus while at the same time defending against microbial pathogens.Failure to demonstrate attenuation of inflammatory responses has been reported to result in various pathologic pregnancy outcomes including spontaneous pre-term labor. Endotoxin tolerance has been associated with protection against tissue injury and even mortality in several different disease models.…”

mentioning

confidence: 99%

“…Endotoxin tolerance has been associated with protection against tissue injury and even mortality in several different disease models. [21][22][23][24][25] During pregnancy, the maternal-fetal interface must provide a unique balance between immunosuppression in order to maintain the pregnancy and prevent rejection of the fetus while at the same time defending against microbial pathogens.Failure to demonstrate attenuation of inflammatory responses has been reported to result in various pathologic pregnancy outcomes including spontaneous pre-term labor. [26][27][28][29] Endotoxin tolerance has been suggested as a possible mechanism to prevent or limit infection-induced immune responses during pregnancy to prevent adverse fetal/neonatal outcomes and premature labor.…”

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confidence: 99%

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Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance

Kim

Maloney

Klimova

et al. 2019

American J Rep Immunol

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Problem Placental infection induces increased levels of pro‐inflammatory cytokines, which have been implicated in the pathogenesis of pre‐term labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study was to determine whether repeated exposure to endotoxin will induce a tolerant phenotype in normal human second‐trimester placental tissue. Methods of study Human second‐trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24 hours, the media was collected for analysis, and the explants were re‐exposed to LPS after adding fresh media for another 24 hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels. Results The first LPS treatment stimulated the secretion of the pro‐inflammatory cytokines IL‐1β and TNF‐α. However, their production was significantly diminished with repeated LPS doses. Production of the anti‐inflammatory cytokines, IL‐1ra and IL‐10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro‐inflammatory cytokines. The ratios of the anti‐inflammatory/pro‐inflammatory mediators (IL‐1ra/IL‐1β and IL‐10/TNF‐α) indicate a progressively more anti‐inflammatory milieu with repeated LPS doses. Conclusion Repeated LPS exposure of human second‐trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal‐fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.

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Section: Discussionmentioning

confidence: 99%

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Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance

Kim

Maloney

Klimova

et al. 2019

American J Rep Immunol

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“…Both in vivo and in vitro studies have proven that preconditioning acts through the endoplasmic reticulum with minor insults of stress stimulating a protective adaptive UPR promoting tolerance and anti-apoptotic signaling fostering resistance to the apoptotic processes associated with subsequent, more damaging stresses 18 , 27 . This preconditioning phenomenon is strongly conserved in evolution 28 and can be induced by many and varied perturbations such as stress-mediated inflammation, hypoxia, and cytotoxins 18 , 29 , 30 . Prior to this study, data pertaining to the role of preconditioning the uterine UPR in the regulation of gestational length was limited.…”

Section: Discussionmentioning

confidence: 99%

Preconditioning the uterine unfolded protein response maintains non-apoptotic Caspase 3-dependent quiescence during pregnancy

et al. 2018

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The prevention of apoptotic caspase 3 activation through biological preconditioning, mediated through the modulation of the unfolded protein response has been demonstrated to ameliorate multiple pathophysiologies. The maintenance of non-apoptotic caspase 3 activity by the unfolded protein response within the pregnant uterus has previously been proven to be critical in inhibiting uterine myocyte contractility during pregnancy. Here we report that the pregnant uterus utilizes an unfolded protein response-preconditioning paradigm to conserve myometrial caspase 3 in a non-apoptotic state in order to effectively inhibit uterine contractility thereby preventing the onset of preterm labor. In the absence of appropriate endogenous preconditioning during pregnancy, uterine caspase 3 is transformed from a non-apoptotic to an apoptotic phenotype. Apoptotic caspase 3 activation results in the precocious triggering of local uterine inflammatory signaling and prostaglandin production, consequently resulting in an increased incidence of preterm birth. These findings represent a paradigm shift in our understanding of how preconditioning promotes the maintenance of uterine non-apoptotic caspase 3 action during pregnancy preventing the onset of premature uterine contraction and therefore defining the timing of the onset of labor.

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“…In this phase, large amounts of endotoxins, which are also termed lipopolysaccharide, were released from ectopic intestinal bacteria because of splanchnic congestion, thus harming liver graft through activated Kupffer cells and numerous mediators of inflammation [6,7]. On the other hand, prolonged anhepatic phase can also indicate prolonged ischemia of donor liver, aggravating ischemia-reperfusion injury, causing tissue injury, and even threatening donor liver function [8,9].…”

Section: Shvc and Shortening Anhepatic Phasementioning

confidence: 99%

Operative Techniques, Treatment, and Precaution of Common Complications of Orthotopic Rat Liver Transplantation

Tang¹,

Wang²,

Gong³

2017

AJMR

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Objective This study investigates operative techniques, treatment, and precaution for common complications of orthotopic liver transplantation (OLT) in rats. Methods OLT was performed in 110 rats through modified two-cuff method. Operative techniques were concluded, and causes, treatment, and precaution of common complications were analyzed. Results In operation phase, main causes for rat death included anesthesia, airway obstruction, pneumothorax, hemorrhagic shock, long anhepatic time, and air embolism. After surgery, main causes for rat death were as follows: stoma bleeding, infection, obstruction, and necrosis of biliary tract and poor hepatic function restoration. Conclusion Improving operative techniques, modifying operative methods, and familiarizing with common complications can reduce occurrence of complications, heighten operative successful rate, and establish more stable models of OLT in rats.

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Endotoxin Tolerance Attenuates Liver Ischemia/Reperfusion Injury by Down-Regulation of Interleukin-1 Receptor-Associated Kinase 4 in Kupffer Cells

Cited by 15 publications

References 18 publications

Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance

Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance

Preconditioning the uterine unfolded protein response maintains non-apoptotic Caspase 3-dependent quiescence during pregnancy

Operative Techniques, Treatment, and Precaution of Common Complications of Orthotopic Rat Liver Transplantation

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