scholarly journals Lipopolysaccharide-Induced Biliary Factors Enhance Invasion of Salmonella enteritidis in a Rat Model

2000 ◽  
Vol 68 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Abul F. M. W. Islam ◽  
Nathan D. Moss ◽  
Yung Dai ◽  
Murray S. R. Smith ◽  
Andrew M. Collins ◽  
...  
Keyword(s):  
Rat Model ◽  
Inflammatory Mediators ◽  
Salmonella Enteritidis ◽  
Bacterial Invasion ◽  
Mesenteric Lymph Nodes ◽  
Necrosis Factor Alpha ◽  
Lps Challenge ◽  
Hepatobiliary System ◽  
Duct Ligation ◽  
Tnf Α

ABSTRACT In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 106to 107 CFU of S. enteritidis led to widespread tissue invasion after days. If animals were similarly challenged after intravenous administration of S. enteritidis LPS (3 to 900 μg/kg of body weight), significant invasion of the livers and mesenteric lymph nodes (MLN) occurred within 24 h, with invasion of the liver increasing in a dose-dependent fashion (P< 0.01). If bile was prevented from reaching the intestine by bile duct ligation or cannulation, bacterial invasion of the liver and MLN was almost totally abrogated (P < 0.001). As i.v. challenge with LPS could induce the delivery of inflammatory mediators into the bile, biliary tumor necrosis factor alpha (TNF-α) concentrations were measured by bioassay. Biliary concentrations of TNF-α rose shortly after LPS challenge, peaked with a mean concentration of 27.0 ng/ml at around 1 h postchallenge, and returned to baseline levels (3.1 ng/ml) after 2.5 h. Although TNF-α cannot be directly implicated in the invasion process, we conclude that the invasiveness of the enteric pathogen S. enteritidis is enhanced by the presence of LPS in the blood and that this enhanced invasion is at least in part a consequence of the delivery of inflammatory mediators to the gastrointestinal tract by the hepatobiliary system.

Differential Effects of Corticosteroids on The Expression of Cyclooxygenase-2, Tumour Necrosis Factor-Alpha and Matrix Metalloproteinase-9 in An Animal Model of Migraine

Cephalalgia ◽  
2008 ◽  
Vol 28 (11) ◽  
pp. 1179-1187 ◽  
Author(s):  
G-M Kim ◽  
K-S Jin ◽  
C-S Chung
Keyword(s):  
Animal Model ◽  
Inflammatory Mediators ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Cox 2 ◽  
Metalloproteinase 9 ◽  
Necrosis Factor

Nitric oxide (NO) directly activates trigeminal afferents innervating the dura mater and up-regulates inflammatory mediators. We evaluated NO-mediated up-regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9), and the effect of glucocorticoid administration in an experimental animal model of migraine. COX-2 and TNF-α expression and MMP-9 activity were increased after continuous intravenous infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence staining demonstrated strong expression of these inflammatory mediators in the meningeal blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was reversed by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-α expression was not affected by MP or RU486 administration. These results suggest proinflammatory mediators are involved in the NO-mediated cascade of migraine pathogenesis. Further understanding of the activation of these inflammatory mediators at the transcriptional level may have therapeutic implications for future migraine treatments.

scholarly journals Differentiation of Monocytes to Macrophages Primes Cells for Lipopolysaccharide Stimulation via Accumulation of Cytoplasmic Nuclear Factor κB

1999 ◽  
Vol 67 (11) ◽  
pp. 5573-5578 ◽  
Author(s):  
Shogo Takashiba ◽  
Thomas E. Van Dyke ◽  
Salomon Amar ◽  
Yoji Murayama ◽  
Aubrey W. Soskolne ◽  
...  
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Necrosis Factor Alpha ◽  
Lps Challenge ◽  
Differentiated Cells ◽  
Human Monocytic Cell Line ◽  
Tnf Α

ABSTRACT During infection, circulating blood monocytes migrate from the vasculature to the extravascular compartments where they mature into tissue macrophages. The maturation process prepares the cell to actively participate in the inflammatory and the immune responses, and many transcription factors have been found to be involved. Here we report on a novel role for nuclear factor κB (NF-κB) in this process. Its accumulation in the cytoplasm of differentiated macrophages is responsible for the enhanced ability of the cell to respond to lipopolysaccharide (LPS) stimulation, as determined by tumor necrosis factor alpha (TNF-α) secretion. Differentiation of the human monocytic cell line THP-1 into macrophage-like cells was induced by exposure of the cells to phorbol myristate acetate. DNA-bindable NF-κB was not detected in the cytoplasm of undifferentiated THP-1 cells but accumulated in the cytoplasm of the cells following differentiation. No TNF-α was detected in the media of resting differentiated and nondifferentiated THP-1 cells. Stimulation with LPS of differentiated cells induced the production of higher levels of TNF-α than stimulation of nondifferentiated cells. This hyperresponsiveness to LPS was found in the mRNA and secreted TNF-α levels. Furthermore, stimulation with LPS induced the translocation of NF-κB from the cytoplasm into the nucleus. This translocation process was more rapid in the differentiated cells than in the nondifferentiated cells, and the resultant accumulated levels of NF-κB in the nucleus were higher. The DNA-bindable NF-κB was identified as a heterodimer of p65 and p50. The results suggest that NF-κB accumulation in the cytoplasm during maturation of monocytes to macrophages primes the cells for enhanced responsiveness to LPS and results in the rapid secretion of inflammatory mediators, such as TNF-α, by mature macrophages following LPS challenge.

scholarly journals Activation of Interleukin-1 Receptor-Associated Kinase by Gram-Negative Flagellin

2001 ◽  
Vol 69 (7) ◽  
pp. 4424-4429 ◽  
Author(s):  
Marlena A. Moors ◽  
Liwu Li ◽  
Steven B. Mizel
Keyword(s):  
Cell Line ◽  
Salmonella Enteritidis ◽  
Mutant Cell ◽  
Interleukin 1 ◽  
Central Component ◽  
No Production ◽  
Gram Negative Bacteria ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Tnf Α

ABSTRACT Flagellin from various species of gram-negative bacteria activates monocytes to produce proinflammatory cytokines. We have analyzed the pathway by which Salmonella enteritidis flagellin (FliC) activates murine and human monocyte/macrophage-like cell lines. Since lipopolysaccharide (LPS), the principal immune stimulatory component of gram-negative bacteria, is known to signal through Toll-like receptor 4 (TLR4), we tested the possibility that FliC also signals via TLR4. When murine HeNC2 cells were stimulated with LPS in the presence of a neutralizing anti-TLR4 monoclonal antibody, tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) production were markedly reduced. In contrast, FliC-mediated TNF-α and NO production were minimally affected by the anti-TLR4 antibody. Furthermore, FliC, unlike LPS, stimulated TNF-α production in the TLR4 mutant cell line, GG2EE, indicating that TLR4 is not essential for FliC-mediated signaling. To test the possibility that FliC signals via another TLR, we measured FliC-mediated activation of interleukin-1 (IL-1) receptor-associated kinase (IRAK), a central component in IL-1R/TLR signaling. FliC induced IRAK activation in HeNC2 and GG2EE cells as well as in the human promonocytic cell line THP-1. IRAK activation was rapid in HeNC2 cells, with maximal activity observed after 5 min of treatment with FliC. In addition, FliC-mediated IRAK activation exhibited the same concentration dependence as was demonstrated for the induction of TNF-α. These results represent the first demonstration of IRAK activation by a purified bacterial protein and strongly suggest that a TLR distinct from TLR4 is involved in the macrophage inflammatory response to FliC.

scholarly journals Microfilariae of the Filarial Nematode Litomosoides sigmodontis Exacerbate the Course of Lipopolysaccharide-Induced Sepsis in Mice

2008 ◽  
Vol 76 (4) ◽  
pp. 1668-1677 ◽  
Author(s):  
Marc P. Hübner ◽  
Bastian Pasche ◽  
Svetoslav Kalaydjiev ◽  
Peter T. Soboslay ◽  
Andreas Lengeling ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Inflammatory Responses ◽  
Interleukin 12 ◽  
Female Adult ◽  
Necrosis Factor Alpha ◽  
Lps Challenge ◽  
Litomosoides Sigmodontis ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from prepatent infections, worms which have not yet started to release microfilariae, developed lower levels of proinflammatory cytokines in the peripheral blood after LPS challenge than sham-treated controls, demonstrating that female adult worms can mitigate the innate immune response. The presence of microfilariae in mice, however, through either direct injection or implantation of microfilaria-releasing adult female worms, turned the LPS challenge fatal. This lethal outcome was characterized by increased plasma levels of gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), and IL-6, greater numbers of macrophages and granulocytes in the peripheral blood, and decreased body temperatures in microfilaria-infected mice. Microfilaria-infected mice deficient in IFN-γ receptor and TNF receptor 1 had increased survival rates after LPS challenge compared to immune-competent mice, suggesting that microfilariae worsen LPS-induced sepsis through actions of IFN-γ and TNF-α. In summary, we have demonstrated that infection of mice with L. sigmodontis female adult worms from prepatent infections protects mice injected with LPS whereas microfilariae worsen LPS-induced sepsis through the induction of proinflammatory cytokines and upregulation of granulocytes, NK cells, and monocytes in the peripheral blood.

scholarly journals Suppression of Murine Endotoxin Response by E5531, a Novel Synthetic Lipid A Antagonist

1998 ◽  
Vol 42 (11) ◽  
pp. 2824-2829 ◽  
Author(s):  
Seiichi Kobayashi ◽  
Tsutomu Kawata ◽  
Akifumi Kimura ◽  
Kaname Miyamoto ◽  
Koichi Katayama ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lipid A ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Necrosis Factor Alpha ◽  
In Vivo Models ◽  
Lps Challenge ◽  
Tnf Α

ABSTRACT As a consequence of blood-borne bacterial sepsis, endotoxin or lipopolysaccharide (LPS) from the cell walls of gram-negative bacteria can trigger an acute inflammatory response, leading to a series of pathological events and often resulting in death. To block this inflammatory response to endotoxin, a novel lipid A analogue, E5531, was designed and synthesized as an LPS antagonist, and its biological properties were examined in vitro and in vivo. In murine peritoneal macrophages, E5531 inhibited the release of tumor necrosis factor alpha (TNF-α) by Escherichia coli LPS with a 50% inhibitory concentration (IC50) of 2.2 nM, while E5531 elicited no significant increases in TNF-α on its own. In support of a mechanism consistent with antagonism of binding to a cell surface receptor for LPS, E5531 inhibited equilibrium binding of radioiodinated LPS ([125I]2-(r-azidosalicylamido)-1, 3′-dithiopropionate-LPS) to mouse macrophages with an IC50 of 0.50 μM. E5531 inhibited LPS-induced increases in TNF-α in vivo when it was coinjected with LPS into C57BL/6 mice primed with Mycobacterium bovis bacillus Calmette-Guérin (BCG). In this model, the efficacy of E5531 was inversely correlated to the LPS challenge dose, consistent with a competitive antagonist-like mechanism of action. Blockade of the inflammatory response by E5531 could further be demonstrated in other in vivo models: E5531 protected BCG-primed mice from LPS-induced lethality in a dose-dependent manner and suppressed LPS-induced hepatic injury in Propionibacterium acnes-primed or galactosamine-sensitized mice. These results argue that the novel synthetic lipid A analogue E5531 can antagonize the action of LPS in in vitro and suppress the pathological effects of LPS in vivo in mice.

scholarly journals Campylobacter jejuni Induces Maturation and Cytokine Production in Human Dendritic Cells

2006 ◽  
Vol 74 (5) ◽  
pp. 2697-2705 ◽  
Author(s):  
Lan Hu ◽  
Mechelle D. Bray ◽  
Manuel Osorio ◽  
Dennis J. Kopecko
Keyword(s):  
Dendritic Cells ◽  
Campylobacter Jejuni ◽  
Cytokine Production ◽  
Diarrheal Disease ◽  
Inflammatory Responses ◽  
Bacterial Invasion ◽  
Microbial Infection ◽  
Necrosis Factor Alpha ◽  
Adaptive Immune ◽  
Tnf Α

ABSTRACT Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in both developed and developing nations. Colonic mucosal invasion and the resulting host inflammatory responses are thought to be the key contributing factors to the dysenteric form of this disease. Dendritic cells (DCs) play an important role in both the innate and adaptive immune responses to microbial infection. In this study, the interaction between human monocyte-derived dendritic cells and C. jejuni was studied. We found that C. jejuni was readily internalized by DCs over a 2-h period. However, after a prolonged infection period (24 or 48 h) with C. jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of dendritic cells over 24 h, as indicated by up-regulation of cell surface marker proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered activation of NF-κB and significantly stimulated production of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis factor alpha (TNF-α) compared to uninfected DCs. Active bacterial invasion of DCs was not necessary for the induction of these cytokines, as heat-killed C. jejuni stimulated similar levels of cytokine production as live bacteria. Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for the increased production of cytokines by DCs. Taken together, these data indicate that during infection, Campylobacter triggers an innate inflammatory response through increased production of IL-1β, IL-6, IL-8, and TNF-α and initiates a Th1-polarized adaptive immune response as predicted from the high level of production of IL-12.

scholarly journals Human Models of Low-Grade Inflammation: Bolus versus Continuous Infusion of Endotoxin

2007 ◽  
Vol 14 (3) ◽  
pp. 250-255 ◽  
Author(s):  
S. Taudorf ◽  
K. S. Krabbe ◽  
R. M. G. Berg ◽  
B. K. Pedersen ◽  
K. Møller
Keyword(s):  
Continuous Infusion ◽  
Inflammatory Mediators ◽  
Low Dose ◽  
Bolus Injection ◽  
In Vivo Model ◽  
Low Grade ◽  
Necrosis Factor Alpha ◽  
Endotoxin Infusion ◽  
Tnf Α ◽  
Low Grade Inflammation

ABSTRACT Systemic low-grade inflammation is recognized in an increasing number of chronic diseases. With the aim of establishing an experimental human in vivo model of systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (0.3 ng/kg of body weight) either as a bolus injection or as a 4-h continuous intravenous infusion, as well as after saline administration, in 10 healthy male subjects on three separate study days. Only bolus endotoxin caused an increase in heart rate, whereas a slight increase in rectal temperature was observed in both endotoxin groups. Tumor necrosis factor alpha (TNF-α), interleukin-6, and neutrophil responses were earlier and more pronounced in the bolus trial compared with the infusion trial results, whereas lymphocytes increased after endotoxin bolus injection as well as infusion without any difference between groups. Finally, endotoxin activated the hypothalamo-pituitary-adrenal axis slightly earlier in the bolus compared to the infusion trial. The continuous endotoxin infusion model may be more representative of human low-grade inflammation than the bolus injection model due to a less dynamic and more sustained increase in circulating levels of inflammatory mediators over time. In conclusion, low-dose endotoxin infusion elicits an inflammatory response, as assessed by a rise in TNF-α, and the responses are significantly different according to whether low-dose endotoxin is applied as a bolus injection or as a continuous infusion.

scholarly journals The effect of acute ophiobolin A treatment on HO-mediated inflammatory processes

2016 ◽  
Vol 36 (6) ◽  
pp. 594-602 ◽  
Author(s):  
Anikó Pósa ◽  
Renáta Szabó ◽  
Zita Szalai ◽  
Krisztina Kupai ◽  
Zoltán Deim ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Cardiac Tissue ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Inflammatory Processes ◽  
Factor Alpha ◽  
Fungal Secondary Metabolite ◽  
Inflammatory Molecules ◽  
Necrosis Factor

Many microbial and plant-derived metabolites contribute to the production of inflammatory mediators and the expression of pro-inflammatory molecules. Ophiobolin A (OPA) is a fungal secondary metabolite produced by Bipolaris species. The aim of our study was to examine the acute effects of this compound on inflammatory processes. Male Wistar rats were treated with 5% ethanol, 0.01 mg/kg OPA, 0.1 mg/kg OPA and 1.0 mg/kg OPA per os. After 24 h of the administrations, inflammatory mediators such as interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and myeloperoxidase (MPO) enzyme as well as heme oxygenase (HO) activity were measured in both plasma and cardiac tissue, along with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We found that OPA caused a significant elevation in the concentrations of IL-6 and TNF-α, increased MPO activity and decreased HO enzyme activity in the plasma. While OPA induces inflammation in the plasma, it did not change the level of inflammatory mediators in the cardiac tissue and the concentrations of serum ALT and AST. Our findings indicate that rapid release of inflammatory mediators by OPA promotes systemic inflammation. However, this acute OPA treatment does not show toxic effects on the cardiac tissue and the concentrations of liver enzymes.

scholarly journals Secretory Leukoprotease Inhibitor: A Native Antimicrobial Protein in the Innate Immune Response in a Rat Model ofS. aureusKeratitis

2009 ◽  
Vol 2009 ◽  
pp. 1-5 ◽  
Author(s):  
Victor E. Reviglio ◽  
Andres Grenat ◽  
Federico Pegoraro ◽  
Ruben H. Sambuelli ◽  
Tayyib Rana ◽  
...  
Keyword(s):  
Rat Model ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Antimicrobial Protein ◽  
Necrosis Factor Alpha ◽  
Defect Groups ◽  
Tnf Α ◽  
Factor Alpha ◽  
Immunohistochemical Studies ◽  
Necrosis Factor

Purpose. To describe the presence of secretory leukocyte protease inhibitor (SLPI), a cationic peptide with antimicrobial and antiprotease activity in the innate immune reaction in a rat model ofStaphylococcus aureuskeratitis.Methods. Forty female Lewis rats were divided into 2 groups: the infectious keratitis and the epithelial defect groups. Eyes were processed for immunohistochemical studies for SLPI, interleukin-1, interleukin-6, tumor necrosis factor-alpha, and matrix metalloproteinase-8.Results. Immunohistochemical studies confirmed high levels of SLPI, IL-1, IL-6, TNF-α, and MMP-8 expression in eyes withS. aureuskeratitis and with epithelial defects, in contrast to undetectable SLPI expression in the normal control corneas.Conclusions. To our knowledge, this paper is the first to demonstrate the presence of SLPI with increased amounts of proinflammatory cytokines in inflamed and infected corneas.

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