Innate Immune Programing by Endotoxin and Its Pathological Consequences

Morris, Matthew C.; Gilliam, Elizabeth A.; Li, Liwu

doi:10.3389/fimmu.2014.00680

Cited by 177 publications

(212 citation statements)

References 114 publications

(110 reference statements)

Supporting

Mentioning

198

Contrasting

Unclassified

Order By: Relevance

“…In a time-dependent manner, VWR led to attenuations in the liver mRNA expression of known inflammatory markers (24). At 6 h post-LPS, there were attenuations in IL-6 and FST, while at 12 h post-LPS, IL-1␤ was attenuated, which together is indicative of a reduced inflammatory load.…”

Section: Discussionmentioning

confidence: 90%

“…Upon exposure to LPS, an inflammatory cascade is activated both systemically and at a tissue-specific level (1). Initial signaling involves a Toll-like receptor 4 (TLR4)-myeloid differentiation primary response gene 88 (MyD88) interaction that then propagates the inflammatory response (24). Increases in circulating inflammatory factors, such as TNF-␣, IL-6, and IL-1␤, occur rapidly and are regulated by the dose and duration of exposure (21,29,40).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice

Peppler

Anderson

Sutton

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Peppler WT, Anderson ZG, Sutton CD, Rector RS, Wright DC. Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice. Am J Physiol Regul Integr Comp Physiol 310: R934 -R942, 2016. First published February 17, 2016 doi:10.1152/ajpregu.00497.2015.-Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis-induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n ϭ 80, ϳ8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P Ͻ 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-␣, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1␤) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72. lipopolysaccharide; inflammation; liver; physical activity; exercise SEPSIS IS A CONTINUUM OF CLINICAL events defined by the presence of infection and systemic inflammation (18). The worldwide incidence of sepsis was recently estimated at 437 cases per 100,000 person years between 2003 and 2015, with an associated fatality rate of 17% (11). This puts a significant burden on the health care system, and in the United States alone, the direct hospital costs associated with sepsis are over $24 billion (17).The infiltration of a host with both gram-negative and gram-positive bacterial species is often considered to be the cause of acute sepsis (34). LPS from Escherichia coli, a component of gram-negative bacteria, is often used to produce these effects in rodent models. Upon exposure to LPS, an inflammatory cascade is activated both systemically and at a tissue-specific level (1). Initial signaling involves a Toll-like receptor 4 (TLR4)-myeloid differentiation primary response gene 88 (MyD88) interaction that then propagates the inflammatory response (24). Increases in circulating inflammatory factors, such as TNF-␣, IL-6, and IL-1␤, occur rapidly and are regulated by the dose and duration of exposure (21,29,40). Clearance of inflammatory markers begins as early as 8 h post...

show abstract

Section: Discussionmentioning

confidence: 90%

mentioning

confidence: 99%

Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice

Peppler

Anderson

Sutton

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Recent efforts in the field of immunology provided evidence of adaptive characteristics of innate immunity, challenging the dogma that innate immunity is nonspecific. Morris et al (2014) suggested that TLR4 activation by very low doses of endotoxin may program host leukocytes into a low-grade "memory" state, contributing to the pathogenesis of chronic diseases. This is in contrast to findings described earlier in this review that endotoxin-induced activation of TLR4 prior to ischemic events has protective effects (Zacharowski et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

2015

View full text Add to dashboard Cite

“…It binds to LPS-binding protein (LBP) and the Toll-like-receptor (TLR) 4, which leads to the activation of the transcription factor NFκB through the MyD88 and interleukin-receptorassociated kinase (IRAK) signalling pathways [125]. NFκB acts as a spider in the web of inflammatory responses.…”

Section: Virulence Factorsmentioning

confidence: 99%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

View full text Add to dashboard Cite

About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

show abstract

Innate Immune Programing by Endotoxin and Its Pathological Consequences

Cited by 177 publications

References 114 publications

Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice

Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

Aquaporins in Infection and Inflammation

Contact Info

Product

Resources

About