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)

Streptococcus agalactiae (group B streptococcus, GBS) is the major pathogen of neonatal sepsis. In some newborns, GBS sepsis may have a severe course, including septic shock with a high mortality rate, whereas other newborns are colonized with GBS on their surfaces without any clinical signs of bacterial infection. The reason for this discrepancy is far from clear. We sought, in this study, to compare cytokine expression in cord blood mononuclear cells after stimulation with GBS strains isolated from newborns with sepsis, and strains isolated from newborns without any symptoms of invasive infection. Cord blood mononuclear cells were incubated with either heat-killed bacteria of different strains or lipopolysaccharide, respectively. After 6 and 24 h, cells were harvested and cytokine mRNA-expression was analyzed by reverse-transcriptase PCR. Likewise, supernatants were tested for IL-6 and tumor necrosis factor-alpha concentrations by enzyme immunoassay. When comparing IL-6 and tumor necrosis factor-alpha secretion, there were significantly higher IL-6 levels after stimulation with sepsis than with colonizing isolates. Likewise, mRNA expression of IL-6, IL-1 beta, and IL-12p40 was significantly higher after stimulation with sepsis isolates. This was also true when normalizing to cytokine expression after stimulation with lipopolysaccharide. These findings indicate that the different clinical pictures in response to GBS, either septic infection or colonization, might reflect strain-specific properties. If the respective characteristics can be defined, it might become possible to distinguish by molecular methods potentially "dangerous" from "harmless" strains. Moreover, our findings underline the essential role of these cytokines in the pathogenesis of neonatal GBS sepsis.
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PMID:Different cytokine expression in cord blood mononuclear cells after stimulation with neonatal sepsis or colonizing strains of Streptococcus agalactiae. 1132 54

The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected with the LP-BM5 retrovirus had a reduced capacity to respond to IL-10 in vitro. The ability of IL-10 to inhibit lipopolysaccharide-induced production of tumor necrosis factor (TNF) alpha and IL-6 was significantly reduced in both alveolar and peritoneal macrophages from infected versus uninfected mice. IL-10 hyporesponsiveness was not related to direct infection by the retrovirus, because bone marrow-derived macrophages infected in vitro with LP-BM5 were as responsive to IL-10 as were uninfected bone marrow-derived macrophages. TNF-alpha appeared to contribute to development of IL-10 hyporesponsiveness, because exposure of normal macrophages to TNF-alpha but not interferon-gamma reduced macrophage responsiveness to IL-10. Reverse transcriptase-PCR and flow cytometry demonstrated normal expression of the alpha and beta chains of the IL-10 receptor in macrophages from infected mice, suggesting that IL-10 hyporesponsiveness is not related to a change in receptor expression. The potential role of reduced IL-10 responsiveness in the chronicity of inflammation in this and other diseases is discussed.
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PMID:IL-10 receptor dysfunction in macrophages during chronic inflammation. 1159 Feb

Human endogenous retroviruses (HERVs) have been implicated as causative agents in diseases characterized by inflammation and macrophage activation, such as multiple sclerosis. Because monocyte activation and differentiation influence retroviral transcription and replication, we investigated the contribution of these processes to the expression of four HERV families (HERV-W, HERV-K, HERV-E, and HERV-H) in human monocytes, and autopsied brain tissue from patients with brain diseases associated with increased macrophage activity. Reverse transcriptase-polymerase chain reaction analysis of primary macrophages and U937 monocytoid cells stimulated with phorbol-12-myristate-13-acetate or lipopolysaccharide revealed three- to ninefold increases in HERV-W, HERV-K, and HERV-H RNA levels. In addition, elevated reverse transcriptase activity and HERV RNA were detectable in supernatants from PMA-stimulated U937 cultures, properties that could be attenuated with the inhibitor of monocyte differentiation threonine-lysine-proline. In contrast, stimulation of monocytes decreased or had no effect on HERV-E expression. Compared with controls, HERV-W and HERV-K expression was increased in brain tissue from patients with multiple sclerosis or human immunodeficiency virus infection or AIDS, with concomitant elevated tumor necrosis factor-alpha levels. Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-alpha expression was also evident (2 of 6 cases). The detection of several HERVs in inflammatory brain diseases and the capacity to augment HERV expression in monocytes with compounds that influence cellular activity suggest that increased expression of these viruses is a consequence of increased immune activity rather than causative of distinct diseases.
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PMID:Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases. 1160 92

The lipoxygenase pathway has been implicated in the growth, migration, and contraction of vascular smooth muscle cells (VSMCs). However, the precise type of lipoxygenase present in the vascular wall has not been characterized. In this study, we used a specific reverse-transcriptase polymerase chain reaction method with 2 sets of specific primers on total RNA and polyA (+)RNA of normal human VSMCs prepared from umbilical artery. Two forms of platelet-type 12-lipoxygenase mRNA were present in human VSMCs: the already published form cloned from human erythroleukemia cells and a variant form of platelet-type 12-lipoxygenase, which includes 2 additional sequences consistent with the 2 introns (D and E). This novel form of 12-lipoxygenase poly A (+)RNA was downregulated by lipopolysaccharide (10 ug/ml) and upregulated by epidermal growth factor (100 ng/ml) but was not affected by angiotensin II (10(-7) mol/l). We developed a rabbit anti-human platelet-type 12-lipoxygenase polyclonal antibody directed against a 24-amino acid peptide encoded within exon 4. Western immunoblotting of protein extracted from VSMCs and umbilical artery and platelet extract with this antibody showed a coordinate 110-kDa protein and the already-described 70-kDa band detected in platelets and cord homogenate. Another 120-kDa protein was consistently detected in cord extracts but not in platelet or VSMC homogenates. The immunohistochemistry study performed with the same antibody showed extensive cytoplasmic staining of VSMCs. The specific role of these different forms of platelet-type 12-lipoxygenase is subject to further investigation.
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PMID:A novel form of platelet-type 12-lipoxygenase mRNA in human vascular smooth muscle cells. 1164

Paneth cells in small intestinal crypts secrete microbicidal alpha-defensins in response to bacteria and bacterial antigens (Ayabe, T., Satchell, D. P., Wilson, C. L., Parks, W. C., Selsted, M. E., and Ouellette, A. J. (2000) Nat. Immunol. 1, 113- 38). We now report that the Ca(2+)-activated K(+) channel mIKCa1 modulates mouse Paneth cell secretion. mIKCa1 cDNA clones identified in a mouse small intestinal crypt library by hybridization to human IKCa1 cDNA probes were isolated, and DNA sequence analysis showed that they were identical to mIKCa1 cDNAs isolated from erythroid cells and liver. The genomic organization was found to be conserved between mouse and human IKCa1 as shown by comparisons of the respective cDNA and genomic sequences. Reverse transcriptase-PCR experiments using nested primers amplified mIKCa1 from the lower half of bisected crypts and from single Paneth cells, but not from the upper half of bisected crypts, villus epithelium, or undifferentiated crypt epithelial cells, suggesting a lineage-specific role for mIKCa1 in mouse small bowel epithelium. The cloned mIKCa1 channel was calcium-activated and was blocked by ten structurally diverse peptide and nonpeptide inhibitors with potencies spanning 9 orders of magnitude and indistinguishable from that of the human homologue. Consistent with channel blockade, charybdotoxin, clotrimazole, and the highly selective IKCa1 inhibitors, TRAM-34 and TRAM-39, inhibited (approximately 50%) Paneth cell secretion stimulated by bacteria or bacterial lipopolysaccharide, measured both as bactericidal activity and secreted cryptdin protein, but the inactive analog, TRAM-7, did not block secretion. These results demonstrate that mIKCa1 is modulator of Paneth cell alpha-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens.
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PMID:Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel. 1172 75

Current knowledge implicates pleural mesothelial cells as mainly responsible for inflammatory responses in the pleural space. However, a vast body of recent evidence underscores the important role of fibroblasts in the process of inflammation in several types of tissues. We hypothesize that HPFBs (human pleural fibroblasts) play an important role in pleural responses and also when activated by bacterial endotoxin LPS (lipopolysaccharide), IL-1 beta (interleukin-1 beta), or TNF-alpha (tumor necrosis factor-alpha) release of C-C and C-X-C chemokines-specifically, MCP-1 and IL-8. Our results show that pleural fluid-isolated human fibroblasts release IL-8 and MCP-1 upon stimulation with IL-1 beta, TNF-alpha, and LPS in both a concentration- and time-dependent manner. RT-PCR (reverse-transcriptase-polymerase chain reaction) studies have also confirmed IL-8- and MCP-1-specific mRNA expression in activated pleural fibroblasts. On the time-dependent response curve, IL-8 was found in maximum concentrations at 144 hr, whereas MCP-1 continued to increase even after 196 hr following stimulation. IL-1 beta induced the maximum release of IL-8 (800-fold) and MCP-1 (164-fold), as compared to the controls. TNF-alpha induced a 95-fold increase in IL-8 and an 84-fold increase in MCP-1 levels, as compared to the controls. Collectively, our results show that human pleural fibroblasts contribute to the inflammatory cascade in the pleural space.
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PMID:Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C (interleukin 8) chemokine expression in human pleural fibroblasts. 1198 90

The repair of an injured bronchial epithelial cell (BEC) monolayer requires proliferation and migration of BECs into the injured area. We hypothesized that BEC monolayer injury results in monocyte chemoattractant protein-1 (MCP-1) production, which initiates the repair process. BECs (BEAS-2B from ATCC) were utilized in this study. MCP-1 interacts with CCR2B receptor (CCR2B), resulting in cell proliferation, haptotaxis, and healing of the monolayer. Reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to verify the presence of CCR2B. CCR2B was not merely present but also inducible by interleukin-2 (IL-2) and lipopolysaccharide (LPS). We demonstrated by immunohistochemistry that BECs express MCP-1 after injury and that receptor expression can be regulated by exposure to IL-2 and LPS. Haptotactic migration of cells was enhanced in the presence of MCP-1 and reduced in the presence of CCR2B antibody. This enhanced or depressed ability of the BECs to perform haptotactic migration was shown to be statistically significant (P < 0.05) when compared to controls. Finally, BECs proliferate in response to MCP-1 as proven by electric cell-substrate impedance sensing (ECIS) technology. MCP-1-specific antibodies were shown to neutralize the MCP-1-mediated BEC proliferation. This cascade of events following injury to the bronchial epithelium may provide insight into the mechanism of the repair process.
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PMID:Induction of MCP-1 expression in airway epithelial cells: role of CCR2 receptor in airway epithelial injury. 1207 56

Oestrogen receptor (ER) regulation of gene transcription in neurosecretory and pituitary cells has been proposed as an important mechanism for increased hypothalamic-pituitary-adrenal (HPA) axis responses in females of several mammalian species, including humans. Inbred female Fischer (F344/N) and Lewis (LEW/N) rats have similar oestrogen levels, although Fischer rats exhibit hyper- and Lewis rats hypo-HPA axis responses. The blunted HPA axis response of Lewis rats has been associated with their blunted hypothalamic corticotropin releasing hormone (CRH) expression. To determine if the female CRH expression deficiency in Lewis rats is associated with defective ER expression and regulation, hypothalamic paraventricular nucleus (PVN) transcript levels of CRH and ER were determined under basal conditions and after immune challenge. Microdissected PVN were obtained from control and lipopolysaccharide (LPS) treated Lewis and Fischer rats and CRH, ERalpha and beta mRNA levels were determined by semiquantitative reverse-transcriptase-polymerase chain reaction. In addition, ERalpha and beta protein levels were determined by semiquantitative Western blots. ERalpha and beta mRNA and protein levels in the PVN of control Fischer rats were significantly higher than in control Lewis rats. ERalpha and beta mRNA and protein levels in Fischer rats were reduced by LPS administration at the time of maximal CRH mRNA levels but did not change in Lewis rats, an effect independent of oestrogen levels. These data indicate that defective neuroendocrine HPA axis responses are associated with defective ER expression and regulation in Lewis PVN despite oestrogen concentrations.
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PMID:Lipopolysaccharide-induced oestrogen receptor regulation in the paraventricular hypothalamic nucleus of lewis and Fischer rats. 1242 37

KE-758, an active metabolite of KE-298, is a novel sulfhydryl antirheumatic drug. We analyzed the effect of KE-758 on tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta production by a human monocytes cell line (THP-1 cells), stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). We compared the effects with other thiol-modifying antirheumatic drugs such as D-penicillamine, bucillamine and auranofin. THP-1 cells were treated with IFN-gamma for 16 h and were then exposed to LPS for an additional 6 h (for TNF-alpha detection) or 24 h (for IL-1 beta detection). The amounts of TNF-alpha and IL-1 beta in culture supernatants were measured using enzyme-linked immunosorbent assay. KE-758 and auranofin but not D-penicillamine and bucillamine significantly suppressed both TNF-alpha and IL-1 beta. Auranofin suppressed IL-1 beta production by reducing cellular viability. Reverse transcriptase-polymerase chain reaction analysis revealed that the suppressive effect of KE-758 is based on the inhibition of messenger ribonucleic acid expression of TNF-alpha and IL-1 beta. KE-758 had no effect on p75 and p55 soluble TNF receptor production in IFN-gamma and LPS-stimulated THP-1 cells. Thus, KE-758 inhibits both TNF-alpha and IL-1 beta production and its antirheumatic profile is apparently distinct from that of D-penicillamine, bucillamine and auranofin.
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PMID:KE-758, an active metabolite of the new anti-rheumatic drug KE-298, suppresses production of tumor necrosis factor-alpha and interleukin-1 beta in THP-1, a human monocyte cell line. 1263 95

Chemokines have been implicated in the pathogenesis of many inflammatory processes, including bronchopulmonary dysplasia in mechanically ventilated premature infants. We hypothesized that early expression of the proinflammatory cytokine, tumor necrosis factor alpha (TNFalpha), would be followed by later expression of the downstream chemokine, Grobeta, in the oxygen-injured newborn lung. Reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were used to assess TNFalpha and Grobeta mRNA expression in lung RNA samples from newborn rabbits exposed to > 95% O2 for 8-9 days, followed by 60% O2 for a further 2-4 weeks or from control rabbits exposed to air. Four lung samples per condition were collected every 2 days from day 0 to day 14, and at days 22 and 36. Rabbit alveolar macrophages (AM) stimulated in vitro with bacterial lipopolysaccharide served as positive controls ( n = 8). Grobeta mRNA expression in rabbit lung samples increased with oxygen exposure until day 8, then returned toward baseline levels. This corresponded to previously described elevations in neutrophil number in the lungs. TNFalpha mRNA expression in lung samples was below the limit of detection by RPA and showed no upregulation in hyperoxic lung samples by RT-PCR. TNFalpha activity was assessed in lung lavage ( n = 2 samples per condition per time) using an L929 cell line bioassay and was not increased in hyperoxic animals. The expression of Grobeta mRNA without antecedent or concurrent TNFalpha mRNA expression or activity makes it unlikely that Grobeta in the hyperoxic newborn rabbit lung is elaborated in response to a stimulus by TNFalpha.
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PMID:Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs. 1474 38


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