scholarly journals Prevention by Methylprednisolone of Increased Circulating Tumor Necrosis Factor-alpha Levels and Lung Injury Associated with Systemic Inflammatory Response Syndrome due to Intraperitoneal Hyperthermia

1999 ◽  
Vol 88 (4) ◽  
pp. 771-776 ◽  
Author(s):  
Megumi Sumida ◽  
Hideo Inaba ◽  
Eiji Isawa ◽  
Shigeru Fujimoto ◽  
Toshihiko Satoh ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Systemic Inflammatory Response Syndrome ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Systemic Inflammatory Response ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Shiga Toxin 1-Induced Inflammatory Response in Lipopolysaccharide-Sensitized Astrocytes Is Mediated by Endogenous Tumor Necrosis Factor Alpha

2009 ◽  
Vol 78 (3) ◽  
pp. 1193-1201 ◽  
Author(s):  
Verónica I. Landoni ◽  
Marcelo de Campos-Nebel ◽  
Pablo Schierloh ◽  
Cecilia Calatayud ◽  
Gabriela C. Fernandez ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Tumor Necrosis Factor Alpha ◽  
Shiga Toxin ◽  
Tumor Necrosis ◽  
Brain Inflammation ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Hemolytic-uremic syndrome (HUS) is generally caused by Shiga toxin (Stx)-producing Escherichia coli. Endothelial dysfunction mediated by Stx is a central aspect in HUS development. However, inflammatory mediators such as bacterial lipopolysaccharide (LPS) and polymorphonuclear neutrophils (PMN) contribute to HUS pathophysiology by potentiating Stx effects. Acute renal failure is the main feature of HUS, but in severe cases, patients can develop neurological complications, which are usually associated with death. Although the mechanisms of neurological damage remain uncertain, alterations of the blood-brain barrier associated with brain endothelial injury is clear. Astrocytes (ASTs) are the most abundant inflammatory cells of the brain that modulate the normal function of brain endothelium and neurons. The aim of this study was to evaluate the effects of Stx type 1 (Stx1) alone or in combination with LPS in ASTs. Although Stx1 induced a weak inflammatory response, pretreatment with LPS sensitized ASTs to Stx1-mediated effects. Moreover, LPS increased the level of expression of the Stx receptor and its internalization. An early inflammatory response, characterized by the release of tumor necrosis factor alpha (TNF-α) and nitric oxide and PMN-chemoattractant activity, was induced by Stx1 in LPS-sensitized ASTs, whereas activation, evidenced by higher levels of glial fibrillary acid protein and cell death, was induced later. Furthermore, increased adhesion and PMN-mediated cytotoxicity were observed after Stx1 treatment in LPS-sensitized ASTs. These effects were dependent on NF-κB activation or AST-derived TNF-α. Our results suggest that TNF-α is a pivotal effector molecule that amplifies Stx1 effects on LPS-sensitized ASTs, contributing to brain inflammation and leading to endothelial and neuronal injury.

Tumor Necrosis Factor: Alpha and Beta Subtypes Appear in Circulation during Onset of Sepsis-induced Lung Injury

1991 ◽  
Vol 143 (5_pt_1) ◽  
pp. 1076-1082 ◽  
Author(s):  
Sandra K. Leeper-Woodford ◽  
P. Declan Carey ◽  
Karl Byrne ◽  
John K. Jenkins ◽  
Bernard J. Fisher ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Lung Injury ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

scholarly journals Moderate Dose of Lipopolysaccharide Induces Tumor Necrosis Factor-alpha and Interleukin-6 Production by Human Monocyte-derived Macrophages

2021 ◽  
Vol 9 (A) ◽  
pp. 468-472
Author(s):  
Nuraiza Meutia ◽  
Lokot Donna Lubis ◽  
Eka Roina Megawati
Keyword(s):  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Tumor Necrosis Factor Alpha ◽  
Interleukin 6 ◽  
Tumor Necrosis ◽  
Human Monocyte ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

BACKGROUND: Macrophages have been widely used for in vitro studies. Despite different types and doses of stimulatory agents that have been tested, there is no consensus for the method. AIM: This study was aimed to determine a sufficient dose of lipopolysaccharide (LPS) to stimulate inflammatory response in macrophages. METHODS: Whole blood was collected from four donors after written informed consent. The monocytes were isolated from peripheral blood mononuclear cells and stimulated with macrophage colony-stimulating factor, LPS, and Interferon-gamma for 6 days until differentiated into macrophages. The production of Tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) were quantified after 24-h further stimulation with 100 ng/mL and 2 μg/mL of LPS. RESULTS: Both doses increased TNF-α _production compare to their controls, but not statistically different (p > 0.05). There were also no differences in IL-6 production between treatments, 56.55 ± 32.30 pg/mL and 70.96 ± 65.08 pg/mL, respectively. CONCLUSION: A dose of 100 ng/mL of LPS was sufficient to stimulate inflammatory response in human monocyte-derived macrophages. A 24-h duration of macrophage stimulation was sufficient to observed the production TNF-α.

scholarly journals Tumor Necrosis Factor-alpha utilizes MAPK/NFκB pathways to induce cholesterol-25 hydroxylase for amplifying pro-inflammatory response via 25-hydroxycholesterol-integrin-FAK pathway

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257576
Author(s):  
Swechha M. Pokharel ◽  
Kim Chiok ◽  
Niraj K. Shil ◽  
Indira Mohanty ◽  
Santanu Bose
Keyword(s):  
Transcription Factor ◽  
Tumor Necrosis Factor ◽  
Inflammatory Response ◽  
Cell Surface ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Wide Spectrum ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Exaggerated inflammatory response results in pathogenesis of various inflammatory diseases. Tumor Necrosis Factor-alpha (TNF) is a multi-functional pro-inflammatory cytokine regulating a wide spectrum of physiological, biological, and cellular processes. TNF induces Focal Adhesion Kinase (FAK) for various activities including induction of pro-inflammatory response. The mechanism of FAK activation by TNF is unknown and the involvement of cell surface integrins in modulating TNF response has not been determined. In the current study, we have identified an oxysterol 25-hydroxycholesterol (25HC) as a soluble extracellular lipid amplifying TNF mediated innate immune pro-inflammatory response. Our results demonstrated that 25HC-integrin-FAK pathway amplifies and optimizes TNF-mediated pro-inflammatory response. 25HC generating enzyme cholesterol 25-hydroxylase (C25H) was induced by TNF via NFκB and MAPK pathways. Specifically, chromatin immunoprecipitation assay identified binding of AP-1 (Activator Protein-1) transcription factor ATF2 (Activating Transcription Factor 2) to the C25H promoter following TNF stimulation. Furthermore, loss of C25H, FAK and α5 integrin expression and inhibition of FAK and α5β1 integrin with inhibitor and blocking antibody, respectively, led to diminished TNF-mediated pro-inflammatory response. Thus, our studies show extracellular 25HC linking TNF pathway with integrin-FAK signaling for optimal pro-inflammatory activity and MAPK/NFκB-C25H-25HC-integrin-FAK signaling network playing an essential role to amplify TNF dependent pro-inflammatory response. Thus, we have identified 25HC as the key factor involved in FAK activation during TNF mediated response and further demonstrated a role of cell surface integrins in positively regulating TNF dependent pro-inflammatory response.

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