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

Co-stimulatory factors are involved in different forms of brain pathology and play an important role in the activation of T-cells. In the current study, we explored the regulation of B7.2, a prominent member of the B7 family of costimulatory factors, in the facial motor nucleus (FMN) following facial axotomy and systemic application of lipopolysaccharide (LPS, endotoxin) using light and electron immunohistochemistry and cytokine-receptor-deficient mice. Facial axotomy led to a gradual increase of B7.2 immunoreactivity (IR) on microglial cell surface; similar effects were also observed following application of LPS, but both effects were not additive, suggesting overlapping or saturated signaling pathways. Some B7.2-IR was already present on activated microglia surrounding injured neurons at days 1-4 after injury, but became particularly intense during neuronal cell death, peaking at day 14. Previous studies revealed that these late microglial changes are accompanied by a strong increase in the expression of proinflammatory cytokines such as interleukin-1 beta (IL1beta) tumor necrosis factor-alpha (TNFalpha) and interferon gamma (IFNgamma) [J. Neurosci. 18 (1998a) 5804]. Here, deletion of the receptors for these cytokines-IL1R1, TNFR1 or TNFR2, but not IFNgammaR1-caused a strong and significant reduction in B7.2-IR in reactive microglial cells, compared with their wild type (WT) controls on the same genetic strain background, with a 31% decrease in IL1R1-/- , 39% in TNFR1-/- and 49% in TNFR2-/- mice. These data underscore the significance of IL1beta, TNFalpha and LPS, and their receptors, as potent inflammatory signals that regulate the cellular response in the injured brain as well as the interaction with the rapidly recruited immune system. The broad susceptibility of B7.2 regulation to a wide range of different inflammatory signals also points to its role as a sensor of molecular pathology, and a factor that plays an important accessory role in allowing and shaping the microglia/T-cell interaction in the injured central nervous system.
 ...
PMID:B7.2 on activated and phagocytic microglia in the facial axotomy model: regulation by interleukin-1 receptor type 1, tumor necrosis factor receptors 1 and 2 and endotoxin. 1546 4

The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor necrosis factor alpha (TNFalpha) has been shown to enhance primary sensory nociceptive signaling. However, the precise cellular sites of TNFalpha and TNF receptor synthesis are still a matter of controversy. Therefore, we differentiated the neuronal and non-neuronal sites of TNFalpha, TNFR1, and TNFR2 mRNA synthesis in dorsal root ganglion (DRG) of control rats and evaluated how their expression is altered under systemic challenge with LPS. In situ hybridization (ISH), RT-PCR analysis of laser-microdissected cells, and immunocytochemistry revealed absence of TNFalpha from DRG neurons and LPS-induced expression of TNFalpha exclusively in a subpopulation of non-neuronal DRG cells. Using RT-PCR and Northern blotting TNFR1 and TNFR2 mRNAs were found to be constitutively expressed and increased after LPS. TNFR1 mRNA was expressed in virtually all neurons and in non-neuronal cells with increased levels after LPS in both. TNFR2 was exclusively expressed and regulated in non-neuronal cells. RT-PCR analysis of microdissected DRG neurons and of the sensory neuronal cell line F11 confirmed the neuronal expression of TNFR1 and excluded that of TNFR2. Double ISH revealed varying levels of TNFR1 mRNA in virtually all DRG neurons including putative nociceptive neurons coding for calcitonin gene-related peptide, substance P, or vanilloid receptor 1. Taken together, we provide evidence that non-neuronally synthesized TNFalpha may directly act on primary afferent neurons via TNFR1 but not TNFR2. This is likely to be relevant under conditions of inflammatory pain and infections accompanied by widespread TNFalpha synthesis and release and may drive sickness behavior.
 ...
PMID:Cell-specific expression and lipopolysaccharide-induced regulation of tumor necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion. 1550 49

Regulation of the pulmonary host defence mechanism is crucial for protection of the lung without pathological consequences. This is exemplified in the normal lung by the induction of both the pro-inflammatory cytokine TNF-alpha, its receptors and the anti-inflammatory cytokine IL-10 by bacterial lipopolysaccharide (LPS). We have evaluated this mechanism in patients with idiopathic pulmonary fibrosis (IPF). Alveolar macrophages (AM) were obtained by bronchoalveolar lavage from 21 subjects with IPF and 12 healthy volunteers. Constitutive and LPS-stimulated AM production of TNF-alpha, TNF soluble receptors CD120a and CD120b, and IL-10 at the protein and mRNA level were measured by bioassay, ELISA and competitive PCR respectively. AM from IPF subjects were more susceptible to LPS induction of TNF-alpha protein (P = 0.03) and transcription of IL-10 mRNA (P = 0.01) and IL-10R1 (P = 0.01) expression in comparison to controls. In contrast, increased CD120b was present as protein and mRNA compared to controls (P = 0.02). AM from IPF subjects were at least as susceptible to down-regulation of LPS-induced TNF-alpha levels by exogenous IL-10 as normal controls (94% versus 63%). These data suggest that there is dysregulation of LPS-induced TNF-alpha and IL-10 in AM from IPF subjects. Further studies are required to elucidate these observations, which may, in turn, give additional insight into the pathogenesis of this disease.
 ...
PMID:Cultured alveolar macrophages from patients with idiopathic pulmonary fibrosis (IPF) show dysregulation of lipopolysaccharide-induced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) inductions. 1580 1

The classic stimulus for cellular cytokine production is bacterial lipopolysaccharide (endotoxin). It was therefore hypothesized that tumor necrosis factor-alpha (TNF-alpha) may be responsible for pericoronitis. TNF-alpha and its receptors were detected by immunohistochemical staining in third molar pericoronitis in ten patients and ten healthy control samples. The percentage of TNF-alpha positive cells was high in pericoronitis (p = 0.0317). TNF receptors TNF-R1 and TNF-R2 were found in macrophage- and fibroblast-like cells, vascular endothelial cells in post-capillary venules, and basal epithelial cells in pericoronitis, but were only weakly expressed in controls. Increased expression of interleukin-1beta and vascular cell adhesion molecule-1 was found as a biological indicator of TNF-alpha ligand-receptor interaction. Explanted tissues acquired destructive potential upon TNF-alpha stimulation, whereas TNF-alpha blockers controlled it in inflamed tissues. These findings suggest that, in pericoronitis, inflammatory and resident cells produce and respond to potent pro-inflammatory cytokine TNF-alpha, with pathogenic and potential therapeutic relevance.
 ...
PMID:Role of TNF-alpha and its receptors in pericoronitis. 1630 50

The neurotrophic factors, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF), are produced by astrocytes, and are induced by inflammatory stimuli including bacterial lipopolysaccharide and pro-inflammatory cytokines. In this study, we examined the regulatory mechanisms of tumor necrosis factor-alpha (TNF-alpha)-induced production of neurotrophic factors. We show here that cultured astrocytes express both TNF-alpha receptor 1 (TNFR1) and TNFR2, and that activation of these receptors by TNF-alpha promotes expression of both NGF and GDNF. In addition, we observe that not only exogenous TNF-alpha but also TNF-alpha produced by astrocytes induce NGF and GDNF production in astrocytes. These results suggest that an autocrine loop involving TNF-alpha contributes to the production of neurotrophic factors in response to inflammation.
 ...
PMID:The role of TNF-alpha and its receptors in the production of NGF and GDNF by astrocytes. 1695 89

Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine and plays a crucial role in pathogenesis of inflammatory arthritis, such as rheumatoid and septic arthritis. TNFalpha exerts its effect by binding to the extracellular domain of TNF receptor (TNFR) 1 and 2. The amino-terminal portion of the TNFR extracellular domain, known as cysteine rich domain 1 (CRD1), or the pre-ligand binding assembly domain (PLAD), plays an important role in the TNFR signaling pathway. TNFR1 PLAD and TNFR2 PLAD proteins block the actions of TNFalpha by interfering with assembly of the receptor complex required for TNFalpha binding. The TNFR1 PLAD protein have been shown to significantly inhibit inflammatory arthritis, such as arthritis induced by TNFalpha, bacterial DNA, lipopolysaccharide, and collagen. The TNFR1 PLAD protein inhibit nuclear factor (NF)-kappaB activation and osteoclastogenesis triggered by TNFalpha was able to inhibit expression of receptor activator of NF-kappaB (RANK), RANK ligand, matrix metalloproteinase and inducible nitric oxide synthase in collagen-induced arthritis. The TNFR1 PLAD protein could therefore be useful in treatment of inflammatory arthritis.
 ...
PMID:Tumor necrosis factor receptor pre-ligand assembly domain is an important therapeutic target in inflammatory arthritis. 1726 87

Phosphatidic acid (PA) is implicated in pathophysiological processes associated with cellular signaling events and inflammation, which include the expressional regulation of numerous genes. Here, we show that PA stimulation increases matrix metalloproteinase-9 (MMP-9) expression in macrophages through tumor necrosis factor (TNF)-alpha signaling. We performed antibody array analysis on proteins from macrophages stimulated with PA. PA was found to induce the production of TNF-alpha, but not of TNF receptor (TNFR)1 and TNFR2 in a time-dependent manner and stimulated significant, though delayed, MMP-9 expression. PA induced the phosphorylations of both ERK1/2 and p38, but not of c-jun amino-terminal kinase. Moreover, only ERK1/2 inhibition by U0126 suppressed PA-induced TNF-alpha production and MMP-9 expression. Neutralizing TNF-alpha, TNFR1 or TNFR2 antibodies significantly suppressed PA-induced MMP-9 expression, suggesting that the production of TNF-alpha in response to PA preceded the expression of MMP-9. Moreover, lipopolysaccharide-induced PA also led to TNF-alpha release and resulted in MMP-9 expression. Taken together, these observations suggest that PA may play a role in MMP-9 regulation through ERKs/TNF-alpha/TNFRs-dependent signaling pathway.
 ...
PMID:Phosphatidic acid as a regulator of matrix metalloproteinase-9 expression via the TNF-alpha signaling pathway. 1727 29

Inhaled lipopolysaccharide (LPS) induces an inflammatory response that may contribute to the pathogenesis of asthma and other airway diseases. Here we investigate the role of tumour necrosis factor (TNF) receptor-associated factor 1 (TRAF1) in leucocyte recruitment using a model of LPS-induced lung inflammation in mice. TRAF1(-/-) mice are completely deficient in the recruitment of lymphocytes to the lower respiratory tract after inhalation of LPS. Although TRAF1(-/-) mice display normal early accumulation of neutrophils, dendritic cells and monocytes in the alveolar airspace, they have a significantly reduced recruitment of these cells by 24 hr after inhalation of LPS when compared to wild-type (WT) mice. Despite normal expression of the pro-inflammatory cytokines TNF, interleukin-1 (IL-1) and IL-6 after LPS treatment, TRAF1(-/-) mice displayed decreased expression of intercellular adhesion molecule 1, vascular cell adhesion molecule 1, CCL17 and CCL20 in the lungs, when compared to LPS-treated WT mice. These results suggest that TRAF1 facilitates LPS-induced leucocyte recruitment into the lung airways by augmenting the expression of chemokines and adhesion molecules. Mice lacking TNF receptor 1 (TNFR1) but not TNFR2 show a phenotype similar to the TRAF1(-/-) mice, suggesting that TRAF1 may act downstream of TNFR1. Significantly, we use bone marrow chimeras to demonstrate that expression of TRAF1 by cells resident in the lungs, but not by circulating leucocytes, is necessary for efficient LPS-induced recruitment of leucocytes to the lung airways.
 ...
PMID:TRAF1 regulates recruitment of lymphocytes and, to a lesser extent, neutrophils, myeloid dendritic cells and monocytes to the lung airways following lipopolysaccharide inhalation. 1732 85

The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor necrosis factor alpha (TNF-alpha) has been shown to enhance primary sensory nociceptive signaling. However, the precise cellular sites of TNF-alpha and TNF receptors synthesis are still a matter of controversy. Therefore, we focused our study on TNF-alpha, TNFR1, and TNFR2 protein synthesis and expression patterns in sciatic nerve of controls and rats under systemic challenge with LPS. The enzyme-linked immunosorbent (ELISA) assay showed that the protein level of TNF-alpha reached peak at 6 h. Double immunofluorescence revealed that LPS-induced expression of TNF-alpha exclusively located in a subpopulation of Schwann cells, endothelial cells, and macrophages, which increased at late time point in the rat sciatic nerve. Positive staining of TNF receptors were also found in Schwann cells and a few endothelial cells. These observations have demonstrated the production of this proinflammatory cytokine by peripheral nerve glia especially Schwann cells. Synthesized TNF-alpha might directly act on peripheral nerve glia via TNF receptors, but the inherent mechanisms remain unknown. Further studies are needed to confirm the pathogenic role of tumor necrosis factor in the early stage of inflammation.
 ...
PMID:Lipopolysaccharide-induced upregulation of tumor necrosis factor-alpha (TNF-alpha) and TNF receptors in rat sciatic nerve. 1787 66

Glycosylation is one of the most important post-translational modifications. It is clear that the single step of beta-1,4-galactosylation is performed by a family of beta-1, 4-galactosyltransferases (beta-1,4-GalTs), and that each member of this family may play a distinct role in different tissues and cells. beta-1,4-GalT I and V are involved in the biosynthesis of N-linked oligosaccharides. beta-1,4-GalT I and V mRNAs are present in control astrocytes and affected by TNF-alpha and lipopolysaccharide (LPS) stimuli. In this study, we examined the regulatory mechanisms of tumor necrosis factor-alpha (TNF-alpha)-affected production of beta-1,4-GalT I and V mRNAs. We show here that cultured astrocytes express TNF-alpha receptor 1 (TNFR1) and increased slightly after exposure to LPS. TNF-alpha and TNFR2 are not detected in control astrocytes and upregulated significantly with LPS stimulation and that activation of these receptors by TNF-alpha affects expressions of beta-1,4-GalT I and V mRNAs. In addition, we observed that not only exogenous TNF-alpha but also TNF-alpha produced by astrocytes affected beta-1,4-GalT I and V mRNAs production in astrocytes. These results suggest that an autocrine loop involving TNF-alpha contributes to the production of beta-1,4-GalT I and V mRNA in response to inflammation.
 ...
PMID:The role of TNF-alpha and its receptors in the production of beta-1,4 galactosyltransferase I and V mRNAs by rat primary astrocytes. 1791 74


<< Previous 1 2 3 4 5 6 Next >>