Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was done to investigate the influence of Gram-negative and Gram-positive sepsis on the expression of the three isoforms of nitric oxide synthase (NOS) gene in rat liver and kidney. Male Sprague-Dawley rats were treated with lipopolysaccharide (LPS, 10 mg/kg i.v.) as an in vivo model for Gram-negative sepsis or lipoteichoic acid (LTA, 10 mg/kg i.v.) as an in vivo model for Gram-positive sepsis. Animals were killed 12 h and 24 h after i.v. treatment. NOS mRNA of the three isoforms was determined by RNase protection assay. NOS II gene expression was strongly induced after LPS or LTA treatment in rat liver and kidney, indicating the efficacy of this treatment to induce sepsis. We found no change of NOS I gene expression after LPS or LTA injection in rat liver and kidney. NOS III gene expression was increased about 8-fold 12 h and about 5-fold 24 h after induction of sepsis in the rat liver whereas in the kidney there was no significant increase in NOS III gene expression. After correction for length NOS III mRNA was about 4- and 40-fold more abundant 12 h and 24 h after LPS treatment than NOS II mRNA in the liver, respectively. Twelve and 24 h after LTA treatment NOS III mRNA was about 18- and 140-fold more abundant than NOS II in the liver. These findings suggest that NOS III is an even more potent source of NO than NOS II in the liver after stimulation with LPS or LTA.
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PMID:Nitric oxide synthase isoform III gene expression in rat liver is up-regulated by lipopolysaccharide and lipoteichoic acid. 927 56

The innate immune system is in the vanguard of host defenses against infection. Recognition of invasive microbial pathogens is mediated by pattern recognition receptors on the surface of immune cells that recognize pathogen-associated molecular motifs. Considerable progress has been made in recent years in understanding how bacterial products initiate sepsis. In gram-negative sepsis, the LPS-binding protein (LBP), CD14 and the recently identified Toll-like receptor 4 (TLR4) are key molecules for the recognition of endotoxin (lipopolysaccharide, LPS) by cells of the myelomonocytic lineage. In gram-positive sepsis, components of the bacterial cell wall (peptidoglycan, PGN; lipoteichoic acids, LTA) have been shown to activate myeloid cells through an interaction with a receptor complex composed of CD14, TLR2 and perhaps also TLR6 (PGN) or CD14 and TLR4 (LTA). By contrast, gram-positive exotoxins act as superantigens and directly stimulate T lymphocytes by cross-linking the MHC class II of antigen presenting cells to specific chains of the T cell receptor. Immune cells activated by microbial pathogens release numerous effector molecules, which orchestrate the innate and adaptive host defenses. Furthermore, bacteria and microbial toxins directly activate the complement and coagulation systems, which play an important part in the host defensive response. Severe sepsis and septic shock can be viewed as clinical manifestations of a failing innate immune response that ultimately results in an overstimulation of the physiological host response. The pathogenesis of sepsis is far more complex that was initially anticipated. However, combined research efforts of basic scientists and clinical investigators continue to provide critical information for the identification of novel therapeutic targets. The exciting results obtained recently with treatment strategies designed to correct coagulation abnormalities occurring during sepsis are an example of how research may ultimately translate into improved patient care.
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PMID:Pathogenesis of septic shock: implications for prevention and treatment. 1193 63

This study investigated the effect of various structural components of Gram-positive (lipotheichoic acid and protein A) and Gram-negative (porins and lipopolysaccharide) bacteria on human dermal fibroblasts. Fibroblasts are important effector cells which have a potential role in augmenting the inflammatory response in various diseases. In this study we present a profile of TNF-alpha, IL-6 and IL-8, the expression of intercellular adhesion molecules (ICAM-1) and the activation of transcriptional nuclear factor NF-kB and AP-1 in human dermal fibroblasts stimulated by bacterial surface components. Compared to the controls, increased ICAM-1, IL-6 and IL-8 gene expression after stimulation of LPS and porins at 2 and 4 h was more evident than that obtained following stimulation of LTA and PA. Gene expression was also associated with the production of cytokine proteins in culture supernatants. TNF-alpha gene expression remained undetectable. Moreover, LPS and porin treatments determined IkBalpha phosphorylation and degradation in human dermal fibroblasts and the subsequent activation of nuclear factors NF-kB and AP-1. These data suggest the importance of such stimuli in the first step of the inflammatory process, as well as the important role played by fibroblasts in skin inflammatory disease.
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PMID:Bacterial components induce cytokine and intercellular adhesion molecules-1 and activate transcription factors in dermal fibroblasts. 1283 9

Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFalpha. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.
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PMID:Toll-like receptors differentially induce nucleosome remodelling at the IL-12p40 promoter. 1474 21

Toll-like receptors (TLRs) play a major role in the innate immune system for initial recognition of microbial pathogens and pathogen associated components. Nitric oxide (NO) is generated in immune cells in response to microbial stimulation and is involved in pathogenesis and control of infection. We used RT-PCR analysis to examine the TLR expression profile on chicken monocytes and demonstrated these cells express chicken TLR2, 3, 4, 6, and 7. TLR5 was not detected by the TR-PCR. We also investigated the differential induction of NO synthesis in chicken monocytes by TLR agonists, including flagellin (FGN, from Salmonella typhimurium), synthetic lipoprotein Pam3CSK4 (PAM), lipopolysaccharide (LPS, from Salmonella enteritidis), lipoteichoic acid (LTA, from Staphylococcus aureus), the synthetic double stranded RNA analog (poly I:C), the guanosine analog, loxoribine (LOX), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). Our results indicate that there was a vast difference among these agonists for their ability to induce NO production. CpG-ODN and LPS were the most potent stimuli and induced significant quantities of NO in cultured monocytes, whereas LTA stimulated significant NO production only at high concentrations. Other agonists such as FGN and poly I:C stimulated very little NO, while PAM, LOX, and nCpG-ODN (control ODN) did not induce NO production. RT-PCR analysis demonstrated that LPS, LTA, and CpG-ODN induced inducible nitric oxide synthase (iNOS) expression in monocytes; whereas the other agonists did not. The presence of TLRs on chicken monocytes and the differential induction of NO production in chicken monocytes by various TLR agonists suggest the differentiation of signaling pathways downstream of individual TLRs.
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PMID:Profile of Toll-like receptor expressions and induction of nitric oxide synthesis by Toll-like receptor agonists in chicken monocytes. 1609 93

The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (TLR) 2 (lipoteichoic acid; LTA), TLR3 (polyIC), TLR4 (lipopolysaccharide; LPS), TLR5 (flagellin), and TLR9 (CpG-B). Supernatant fluids from the cultures were analyzed for levels of 5 different pro-inflammatory cytokines, interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, and TNF-alpha. After in vitro challenge with TLR ligands, PBC monocytes produced higher relative levels of pro-inflammatory cytokines, particularly IL-1beta, IL-6, IL-8, and TNF-alpha, compared with controls. In conclusion, monocytes from patients with PBC appear more sensitive to signaling via select TLRs, resulting in secretion of selective pro-inflammatory cytokines integral to the inflammatory response that may be critical in the breakdown of self-tolerance.
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PMID:Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis. 1617 22

Due to the discovery of novel surgical techniques and new materials medical devices are increasingly used. Contact of these biomaterials with human tissue or blood commonly leads to inflammation of varying degrees, sometimes resulting in severe health problems. Possible causes are limited biocompatibility or pyrogenic contamination of the material. We adapted the recently validated in vitro pyrogen test (IPT), based on human whole blood cytokine release, to test the safety of biomaterials. Human whole blood is brought into direct contact with the surface of the test material and the release of the pro-inflammatory cytokine IL-1beta is measured. This procedure represents a human-relevant assay allowing the detection of pyrogens of different origins, e.g. Gram-negative (lipopolysaccharide, LPS) or Gram-positive (lipoteichoic acid, LTA), peptidoglycan (cell wall components of most bacteria) and fungal zymosan by direct material contact. The sensitivity of the test system allows a starting concentration of 10 pg/ml for LPS, 10 ng/ml for zymosan and 1 microg/ml for LTA and peptidoglycan from different strains. Furthermore, we have shown that the test for solid materials can be carried out with cryo-preserved blood, which results in an even lower detection limit.
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PMID:An in vitro pyrogen safety test for immune-stimulating components on surfaces. 1715 7

The impaired infection control related to the functional immaturity of the neonatal immune system is an important cause of infection in preterm newborns. We previously reported that constitutive Toll-like receptor (TLR) 4 expression and cytokine secretion on lipopolysaccharide (LPS) stimulation increases with gestational age. Here, we analyzed constitutive monocyte TLR2 expression and evaluated the expression profiles of the proximal downstream adapter molecule myeloid differentiation factor 88 (MyD88). We further investigated activation of protein kinases p38 and extracellular regulated kinsase (ERK) 1/2 in CD14 monocytes after ex vivo stimulation with bacterial TLR ligands (LPS and lipoteichoic acid [LTA]). The functional outcome of the stimulation was determined by cytokine secretion. Monocytes from 31 preterm newborns (<30 weeks of gestation, n=16; 30-37 weeks of gestation, n=15), 10 term newborns, and 12 adults were investigated. In contrast to TLR4 expression, TLR2 levels did not differ between age groups. However, MyD88 levels were significantly lower in preterm newborns. Activation of p38 and ERK1/2 was impaired in all newborn age groups after stimulation with TLR-specific ligands. Accordingly, after LTA stimulation, the levels of interleukin (IL)-1 beta , IL-6, and IL-8 cytokine production were substantially lower (P<.001) in preterm newborns than in adults. The reduced functional response to bacterial cell wall components appears to be part of the functional immaturity of the neonatal immune system and might predispose premature newborns to bacterial infection.
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PMID:Immaturity of infection control in preterm and term newborns is associated with impaired toll-like receptor signaling. 1719 Nov 75

Ethyl pyruvate (EP) is a stable pyruvate derivative that has been shown to exert anti-inflammatory effects in various models of systemic inflammation including endotoxemia. We here sought to determine the local effects of EP, after intrapulmonary delivery, in models of lung inflammation induced by instillation via the airways of either lipopolysaccharide (LPS, a constituent of the gram-negative bacterial cell wall) or lipoteichoic acid (LTA, a component of the gram-positive bacterial cell wall). For this, we first established that EP dose dependently reduced the responsiveness of mouse MH-S alveolar macrophages and mouse MLE-15 and MLE-12 respiratory epithelial cells to stimulation with LPS or LTA in vitro. We then showed that intranasal administration of EP dose dependently inhibited tumor necrosis factor alpha release in bronchoalveolar lavage fluid of mice challenged with either LPS or LTA via the airways. Moreover, EP reduced the recruitment of neutrophils into the bronchoalveolar space after either LPS or LTA administration. These data suggest that intrapulmonary delivery of EP diminishes lung inflammation induced by LPS or LTA, at least in part by targeting alveolar macrophages and respiratory epithelial cells.
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PMID:Intrapulmonary delivery of ethyl pyruvate attenuates lipopolysaccharide- and lipoteichoic acid-induced lung inflammation in vivo. 1757 42

The objective of this study is to test whether the activation of toll-like receptors (TLRs) 2 and 3 (innate immune receptors for gram-positive and viral pathogens, respectively) can induce preterm delivery. One uterine horn of preterm pregnant CD-1 mice at approximately 75% of gestation was injected with TLR-2 ligands (lipoteichoic acid [LTA] or peptidoglycan [PGN]) or the TLR-3 ligand polyinosinic:cytidylic acid (poly[I:C]). Preterm delivery was recorded. In a separate group of mice, tissue mRNAs were quantified by reverse transcriptase polymerase chain reaction 5 hours after treatment with PGN or poly(I:C). Intrauterine PGN and LTA induced preterm delivery, reaching 100% at maximal doses. Intraperitoneal PGN also induced preterm delivery but at lower rates (maximum = 55%). Intrauterine poly(I:C) induced preterm birth in up to 31% of mice. Poly(I:C) induced uterine interferon beta and chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) but not interleukin 1beta, tumor necrosis factor, or lipopolysaccharide-induced CXC chemokine. PGN did not alter these mRNAs when compared with saline. Neither treatment induced gene expression in fetal membranes. Activation of either TLR-2 or -3 can induce preterm delivery in the mouse. Activation of TLR-3 with poly(I:C) induces interferon beta and the chemokine CCL5 in uterine tissues but not in fetal membranes.
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PMID:Activation of toll-like receptors 2 or 3 and preterm delivery in the mouse. 1764 3


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