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)

Evidence is accumulating that interleukin-8 (IL-8), discovered as a potent neutrophil chemotactic factor, plays a crucial role in establishing acute neutrophil-mediated inflammation by exerting various activities against non-leukocytic as well as leukocytic cells. Various types of cells can rapidly produce a large amount of IL-8 upon stimulation with inflammatory stimuli, such as lipopolysaccharide, IL-1, and tumor necrosis factor (TNF). However, IL-8 production is tightly regulated at several levels, particularly at the transcriptional levels to prevent aberrant production. Our previous experiments demonstrated that IL-8 gene transcription requires the cooperative activation of a transcription factor, NF-kappa B, with an additional transcription factor, AP-1 or NF-IL6, depending on types of cells and stimuli. In addition, we recently observed that infection with Helicobacter pylori or cytomegalovirus activated NF-kappa B, therapy inducing IL-8 protein secretion as well as IL-8 gene transcription. Moreover, IL-8, in turn, enhanced cytomegalovirus replication and infectious virion production. Collectively, these results suggest the potential involvement of IL-8 in the pathology of bacterial or viral infection.
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PMID:[Molecular mechanism of interleukin-8 gene expression]. 976 Aug 36

We studied the effect of lipopolysaccharide (LPS) on the proliferation of culture-stimulated rat stellate cells. DNA synthesis as determined by [3H]-thymidine incorporation was significantly suppressed by up to 52% compared with the control culture in the presence of LPS (> 5 ng/mL). Such an inhibitory effect of LPS was dramatically augmented in the presence of interferon-gamma (IFNgamma). Lipopolysaccharide alone or in combination with IFNgamma activated transcription factors AP-1 and NF-kappaB, and elicited nitric oxide (NO) production by stellate cells by inducing NO synthase. Inhibition of NO production by the addition of L-arginine antagonists to the culture, partially cancelled such an inhibitory effect of LPS and/or IFNgamma on DNA synthesis without affecting the activation of AP-1 and NF-kappaB and the NO synthase level. The cellular level of cyclic guanosine monophosphate (cGMP) increased in response to LPS and IFNgamma, and dibutyryl cGMP or 8-bromo-cGMP inhibited the incorporation of [3H]-thymidine in a dose-dependent manner. These results indicate that LPS is potent in modulating stellate cell proliferation by some NO- and cGMP-dependent mechanism.
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PMID:Regulation of stellate cell proliferation by lipopolysaccharide: role of endogenous nitric oxide. 979 29

The gene encoding rat bradykinin B1 receptor has been cloned by using a partial rat B1 cDNA probe. The rat B1 receptor gene contains two exons and the entire coding region is within the second exon. The 5'-flanking region of the rat B1 receptor gene contains several putative transcriptional regulatory sites including TATA box, cAMP response element, NF-kappaB and AP-1. It showed promoter activity inducible by lipopolysaccharide in vascular smooth muscle cells. Rat B1 receptor mRNA was found to be alternatively spliced and induced by lipopolysaccharide treatment in a wide range of tissues, such as the salivary gland, testis, kidney, lung, heart, prostate and aorta. The deduced rat B1 receptor amino acid sequence is 71% homologous to human and rabbit counterparts, and 89% homologous to the mouse counterpart. The expressed B1 receptor in HEK293 cells displayed a rank order of affinity for the kinin peptides: des-Arg9-BK>Lys-des-Arg9-BK approximately des-Arg9, Leu8-BK>Sar-Tyr-epsilonAhx-Lys-[D-betaNal7, Ile8]-des-Arg9-BK>Sar-Tyr-epsilonAhx-Lys-des-Arg9-BK>>BK>> Hoe140. These results indicate that the cloned gene encodes a functional rat B1 receptor.
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PMID:Molecular cloning and expression of rat bradykinin B1 receptor. 980 50

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-kappaB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-alpha, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.
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PMID:Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene. 983 56

Tissue Factor (TF) gene expression is transiently induced in human monocytic THP-1 cells by lipopolysaccharide (LPS). We characterized the transcription factor complexes binding to the TF gene promoter LPS response element (LRE) (-220 to -172), which contains binding sites for nuclear factor kappaB (NFkappaB) and activator protein 1 (AP1) transcription factors, and examined the nature of the activation of these factors during a 24-h time course of LPS stimulation. We found proteolysis of the cytoplasmic inhibitory protein IkappaBalpha and nuclear translocation of the NFkappaB/Rel family proteins p65 and c-Rel, corresponding to the transient binding of a p65/c-Rel heterodimer to the kappaB-like site of the LRE. AP1 binding to the LRE was found to be constitutive, with the majority of the AP1 complexes being JunD/Fra-2 heterodimers. A change in the activation state of the AP1 complexes was, however, found to be transient, as determined by JunD phosphorylation of AP1 bound to the proximal binding site. This directly correlates to the transient activation of Jun N-terminal kinase (SAPK/JNK). These data indicate that LPS induction of TF gene expression in monocytic THP-1 cells is regulated by both the transient phosphorylation of Jun-family proteins and the nuclear translocation and transient binding of NFkappaB/Rel proteins.
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PMID:Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation. 986 53

Nitric oxide production by macrophages is principally regulated by the calcium-independent enzyme, inducible nitric oxide synthase (iNOS). Both lipopolysaccharide and TNF-alpha synergize with IFN-gamma in the expression of iNOS with subsequent production of nitric oxide. Previous work has shown that IL-4 downregulates iNOS and nitric oxide expression by macrophages stimulated with LPS and IFN-gamma. In this study, we found that IL-4 also downregulated iNOS and nitric oxide expression induced by IFN-gamma and TNF-alpha and in mouse macrophages. Because various members of the mitogen-activated protein kinases and their upstream kinases have been shown to directly or indirectly activate a number of transcription factors including AP-1 and NFkappaB, we examined the effects of IL-4 on TNF-alpha activation of the MAPKs. Our results show that IL-4 modestly inhibited JNK/SAPK and ERK activation by TNF-alpha. Previously, we showed that selective pharmacologic inhibition of the ERK and/or p38mapk pathway did not affect NO2- expression. Treatment of cells with the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) showed a dose-response inhibition of NO2- expression. NPPB was also found to inhibit ERK and JNK/SAPK activation but not p38mapk with TNF-alpha stimulation. The discordance between the marked degree of inhibition of iNOS transcript by IL-4 and the modest inhibition of JNK/SAPK and ERK suggests that the mechanism by which IL-4 inhibits iNOS transcription appears more complex than a mere inhibition of these MAPKs.
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PMID:Potential role of the JNK/SAPK signal transduction pathway in the induction of iNOS by TNF-alpha. 991 6

Macrophages are targeted by environmental pollutants and play a role in allergic inflammation. We explored the molecular basis for induction of RANTES (regulated upon activation, normal T-cells expressed and secreted) mRNA by lipopolysaccharide (LPS) and the redox-active quinone, tert-butylhydroxyquinone (tBHQ). We demonstrate that transcriptional activation of the human RANTES promoter by LPS is dependent on specific AP-1 and NF-kappaB response elements, which are regulated by c-Jun N-terminal kinase (JNK) and NF-kappaB kinase cascades, respectively. The transcriptional activation of the TRE3/4 site is mediated through the transcriptional activation of c-Jun by JNK. A c-Jun mutant which lacks a transcriptional activation domain interfered in the activation of the RANTES promoter. Similarly, kinase-inactive NF-kappaB inducing kinase interfered in the activation of the RANTES promoter. While activation of the RANTES promoter could also be blocked by the downstream kinase-inactive IkappaB kinases, only IKKalpha appears to be LPS-inducible. tBHQ also exerted subtle effects on the human RANTES promoter and induced mRNA expression in parallel with generating NF-kappaB shift complexes.
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PMID:Activation of the human RANTES gene promoter in a macrophage cell line by lipopolysaccharide is dependent on stress-activated protein kinases and the IkappaB kinase cascade: implications for exacerbation of allergic inflammation by environmental pollutants. 1007 57

The mechanism by which 2-acetylaminofluorene (AAF) inhibited nitric oxide (NO) formation, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was investigated. The decrease in NO, as demonstrated by measurement of nitrite was found to correlate well with a decrease in inducible nitric oxide synthase (iNOS) mRNA. Since the promoter in iNOS gene contains binding motifs for NF-kappa B/Rel, AP-1, and NF-IL6 which appear to be important for LPS-mediated iNOS induction, the effect of AAF on the activation of these transcription factors was determined. Treatment of AAF to RAW 264.7 cells induced a dose-related inhibition of NF-kappa B/Rel in chloramphenicol acetyltransferase activity, while either AP-1 or NF-IL6 activation was not affected by AAF. Treatment of RAW 264.7 cells with AAF inhibited protein/DNA binding of NF-kappa B/Rel to its cognate site as measured by electrophoretic mobility shift assay. In addition, AAF treatment caused a significant reduction of nuclear c-rel, p65, and p50 protein levels, and this decrease was paralleled by the accumulation of cytoplasmic c-rel, p65, and p50. These data suggest that AAF inhibits iNOS gene expression by a mechanism involving a blockade of LPS-induced nuclear translocation of NF-kappa B/Rel.
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PMID:Acetylaminofluorene inhibits nitric oxide production in LPS-stimulated RAW 264.7 cells by blocking NF-kappa B/Rel activation. 1007 54

We investigated whether vascular endothelial growth factor (VEGF) production by human pulp cells (HPC) is regulated by lipopolysaccharide (LPS) in relation to the pathogenesis of pulpitis. Although HPC incubated with medium alone only marginally expressed VEGF mRNA and produced a low level of VEGF as detected by enzyme-linked immunosorbent assay, the VEGF mRNA expression and VEGF production were markedly enhanced upon stimulation with LPS from Escherichia coli. Prevotella intermedia LPS, phorbol 12-myristate 13-acetate, and interleukin-6 also induced VEGF mRNA expression in HPC. A simian virus 40-infected HPC line also exhibited increased VEGF mRNA expression in response to E. coli LPS, but lung and skin fibroblasts did not. Fetal bovine serum (FBS) increased the sensitivity of HPC to LPS in a dose-dependent manner. HPC did not express membrane CD14 on their surfaces. However, the anti-CD14 monoclonal antibody MY4 inhibited VEGF induction upon stimulation with LPS in HPC cultures in the presence of 10% FBS but not in the absence of FBS. LPS augmented the VEGF production in HPC cultures in the presence of recombinant human soluble CD14 (sCD14). To clarify the mechanisms of VEGF induction by LPS, we examined the possible activation of the transcription factor AP-1 in HPC stimulated with LPS, by a gel mobility shift assay. AP-1 activation in HPC was clearly observed, whereas that in skin fibroblasts was not. The AP-1 inhibitor curcumin strongly inhibited LPS-induced VEGF production in HPC cultures. In addition, a protein synthesis inhibitor, cycloheximide, inhibited VEGF mRNA accumulation in response to LPS. These results suggest that the enhanced production of VEGF in HPC induced by LPS takes place via an sCD14-dependent pathway which requires new protein synthesis and is mediated in part through AP-1 activation.
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PMID:Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture. 1008 96

The involvement of ceramide in lipopolysaccharide-mediated activation of mouse macrophages was studied. Lipopolysaccharide, cell-permeable ceramide analogs, and bacterial sphingomyelinase led to phosphorylation of the extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38 kinase and induced AP-1 DNA binding in C3H/OuJ (Lpsn) but not in C3H/HeJ (Lpsd) macrophages. Lipopolysaccharide and ceramide mimetics showed distinct kinetics of mitogen-activated protein kinase phosphorylation and AP-1 induction and activated AP-1 complexes with different subunit compositions. Lipopolysaccharide-activated AP-1 consisted of c-Fos, Jun-B, Jun-D, and c-Jun, while C2-ceramide induced Jun-D and c-Jun only. Lipopolysaccharide and, less potently, C2-ceramide or sphingomyelinase, stimulated AP-1-dependent reporter gene transcription in RAW 264.7 cells. Unlike lipopolysaccharide, C2-ceramide failed to activate NF-kappaB and did not induce production of tumor necrosis factor or interleukin-6. The lipopolysaccharide antagonist, Rhodobacter sphae-roides diphosphoryl lipid A, inhibited lipopolysaccharide activation of NF-kappaB and AP-1 but did not block C2-ceramide-induced AP-1. Pretreatment of C3H/OuJ macrophages with C2-ceramide greatly diminished AP-1 induction following subsequent C2-ceramide stimulation. However, lipopolysaccharide-induced transcription factor activation and cytokine release were not influenced. In contrast, lipopolysaccharide pretreatment inhibited both lipopolysaccharide- and C2-ceramide-mediated responses. Thus, ceramide partially mimics lipopolysaccharide in activating the mitogen-activated protein kinases and AP-1 but not in mediating NF-kappaB induction or cytokine production, suggesting a limited role in lipopolysaccharide signaling.
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PMID:Limited role of ceramide in lipopolysaccharide-mediated mitogen-activated protein kinase activation, transcription factor induction, and cytokine release. 1009 12


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