The involvement of sphingosine kinase 1 in LPS‐induced Toll‐like receptor 4‐mediated accumulation of HIF‐1α protein, activation of ASK1 and production of the pro‐inflammatory cytokine IL‐6

2010 ◽  
Vol 89 (2) ◽  
pp. 268-274 ◽  
Author(s):  
Dmitri Pchejetski ◽  
Joao Nunes ◽  
Karen Coughlan ◽  
Harjinder Lall ◽  
Stuart M Pitson ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Protein Activation

OR.44. Toll-like Receptor 4 Engagement Blocks Inflammatory Cytokine Production by B Cells from Inflammatory Disease Patients

2009 ◽  
Vol 131 ◽  
pp. S21
Author(s):  
Madhumita Jagannathan ◽  
Hyunjin Shin ◽  
Yue Zhang ◽  
Hatice Hasturk ◽  
Alpdogan Kantarci ◽  
...  
Keyword(s):  
B Cells ◽  
Inflammatory Disease ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Cytokine Production

scholarly journals Propofol Ameliorates Ischemic Brain Injury by Blocking Toll-like Receptor 4-dependent Pathway and Suppressing Consequent Inflammatory Cytokine Production

2020 ◽  
Author(s):  
Kazuha Mitsui ◽  
Masakazu Kotoda ◽  
Sohei Hishiyama ◽  
Ayasa Takamino ◽  
Sho Morikawa ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Cytokine ◽  
Neuroprotective Effect ◽  
Ischemic Brain Injury ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Neuroprotective Effects ◽  
Inflammatory Cytokine Production ◽  
Ischemic Brain ◽  
Dependent Pathway

Abstract BackgroundIschemic stroke is one of the leading causes of mortality and morbidity worldwide. Accumulated evidence suggests that the consequent excessive inflammation plays detrimental roles in the pathogenesis of secondary injury after cerebral infarction and exacerbates the brain tissue damage. Although regulation of the inflammation would be the potential strategy for the novel treatment option, effective methods that control the cerebral inflammation have not yet been established. Recent studies have suggested that propofol, a sedative agent widely used for management of patients with acute stroke, suppresses excessive inflammation and may have neuroprotective effects against ischemic brain injury. However, the available evidence is still limited and controversial, and the underlying mechanism remains unclear. This study aimed to investigate the neuroprotective effects of propofol against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4), the critical mediator of inflammation in the ischemic brain.ResultsTreatment with propofol significantly reduced infarct volume in wild-type mice (7.9 ± 1.4 vs. 12.6 ± 1.1 mm3, n = 10 each, p < 0.05). The propofol-treated mice exhibited lower levels of pro-inflammatory cytokine expressions compared with the control mice (IL-6: 0.57 ± 0.23 vs. 1.00 ± 0.39, p < 0.05, IL-1β: 0.53 ± 0.24 vs. 1.00 ± 0.36, p = 0.087, n = 15 each). The neuroprotective effect of propofol was abrogated by TLR4 gene knockout. Propofol treatment had no significant effects on hemodynamic parameters.ConclusionsPropofol attenuates brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production. This insight into the mechanism underlying the neuroprotective effect of propofol against ischemic brain injury may lead to a new strategy for preventing exacerbation of cerebral infarction.

scholarly journals Potential Role for Toll-Like Receptor 4 in Mediating Escherichia coli Maltose-Binding Protein Activation of Dendritic Cells

2007 ◽  
Vol 75 (3) ◽  
pp. 1359-1363 ◽  
Author(s):  
Stefan Fernandez ◽  
Dupeh R. Palmer ◽  
Monika Simmons ◽  
Peifang Sun ◽  
John Bisbing ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dendritic Cells ◽  
Pathogenic Bacteria ◽  
Binding Protein ◽  
Maltose Binding Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Necrosis Factor Alpha ◽  
Protein Activation ◽  
The Stability

ABSTRACT The Escherichia coli maltose-binding protein (MBP) is used to increase the stability and solubility of proteins in bacterial protein expression systems and is increasingly being used to facilitate the production and delivery of subunit vaccines against various pathogenic bacteria and viruses. The MBP tag is presumed inert, with minimum effects on the bioactivity of the tagged protein or its biodistribution. However, few studies have characterized the immunological attributes of MBP. Here, we analyze the phenotypic and functional outcomes of MBP-treated dendritic cells (DCs) and show that MBP induces DC activation and production of proinflammatory cytokines (interleukin-1β [IL-1β], IL-6, IL-8, tumor necrosis factor alpha, and IL-12p70) within 24 h and strongly increases Iκβ phosphorylation in treated cells. Interestingly, phosphorylation of Iκβ was largely abrogated by the addition of anti-human Toll-like receptor 4 (TLR4) antibodies, indicating that MBP activates signaling for DC maturation via TLR4. Consistent with this hypothesis, MBP activated the TLR4-expressing cell line 293-hTLR4A but not control cultures to secrete IL-8. The observed data were independent of lipopolysaccharide contamination and support a role for TLR4 in mediating the effects of MBP. These results provide insight into a mechanism by which MBP might enhance immune responses to vaccine fusion proteins.

Physical Activity Status, but not Age, Influences Inflammatory Cytokine Production and Toll-like Receptor 4

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S308 ◽  
Author(s):  
Brian K. McFarlin ◽  
Michael G. Flynn ◽  
Wayne W. Campbell ◽  
Bruce A. Craig ◽  
J. P. Robinson ◽  
...  
Keyword(s):  
Physical Activity ◽  
Inflammatory Cytokine ◽  
Cytokine Production ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Inflammatory Cytokine Production

scholarly journals Toll-like Receptor 4 Modulation as a Strategy to Treat Sepsis

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
X. Wittebole ◽  
D. Castanares-Zapatero ◽  
P. F. Laterre
Keyword(s):  
Inflammatory Cytokine ◽  
Causes Of Death ◽  
Potential Role ◽  
Signalling Pathways ◽  
Gram Negative Bacteria ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Therapeutic Targeting ◽  
Sepsis And Septic Shock

Despite a decrease in mortality over the last decade, sepsis remains the tenth leading causes of death in western countries and one of the most common cause of death in intensive care units. The recent discovery of Toll-like receptors and their downstream signalling pathways allowed us to better understand the pathophysiology of sepsis-related disorders. Particular attention has been paid to Toll-like receptor 4, the receptor for Gram-negative bacteria outer membrane lipopolysaccharide or endotoxin. Since most of the clinical trial targeting single inflammatory cytokine in the treatment of sepsis failed, therapeutic targeting of Toll-like receptor 4, because of its central role, looks promising. The purpose of this paper is to focus on the recent data of various drugs targeting TLR4 expression and pathway and their potential role as adjunctive therapy in severe sepsis and septic shock.

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