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)

Neutrophil apoptosis leads to macrophage ingestion of intact senescent neutrophils. This may represent a neutrophil removal mechanism that is important both in the control of inflammatory tissue injury and for the normal resolution processes of inflammation. Because apoptosis is likely to be a key control process in cell and tissue homeostasis, a number of inflammatory mediators were tested for their ability to modulate the rate of apoptosis in populations of neutrophils aging in culture. Endotoxic lipopolysaccharide, human recombinant complement factor 5a, and human recombinant granulocyte-macrophage colony-stimulating factor all markedly inhibited the rate of neutrophil apoptosis in a concentration-dependent fashion, without inducing necrosis (as assessed by trypan blue exclusion). This inhibitory effect on the rate of neutrophil apoptosis was shown by morphological criteria and confirmed by gel electrophoresis of extracted DNA. Inhibition of apoptosis of aging neutrophil populations was associated with prolongation of the functional life span of the population as assessed by the ability of neutrophils to spread on glass surfaces, to polarize in response to deliberate stimulation with N-formyl-Met-Leu-Phe (fMLP), and to release the granule enzyme marker myeloperoxidase on fMLP stimulation. These observations show that inflammatory mediators prolong the functional life span of neutrophils through modulation of apoptosis. Further elucidation of these mechanisms will lead to a better understanding of the processes controlling neutrophil residence and function in inflamed tissues and may provide further insights into the molecular mechanisms of apoptosis, which is of widespread importance in tissue biology.
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PMID:Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. 840 50

The concentration of plasma angiotensinogen increases upon induction of inflammation. Studies were carried out using serum samples collected from mice and rats after injection of lipopolysaccharide (LPS) to determine whether interleukin-6 (IL-6) is a mediator responsible for the inflammation-induced increase of angiotensinogen synthesis in liver cells. Serum collected from mice or rats 2 and 4 hr after injection of LPS contained a factor that stimulated [35S]methionine incorporation into angiotensinogen newly synthesized by rat hepatoma H4IIEC3 (H4) cells. Assay of IL-6 using an IL-6-dependent murine hybridoma, MH60.BSF2 cells, showed the presence of IL-6-like activity in sera of mice or rats 2 and 4 hr after injection of LPS. Anti-mouse IL-6 monoclonal antibody completely inhibited not only the IL-6-like activity present in LPS-treated mouse serum but also the ability of the serum to stimulate angiotensinogen synthesis of H4 cells. These results suggest that increased synthesis of angiotensinogen in the liver after induction of inflammation is mediated by IL-6, a cytokine important in immune reactions and the hepatic acute-phase response.
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PMID:Interleukin-6 as a mediator responsible for inflammation-induced increase in plasma angiotensinogen. 842 13

The humoral response to Salmonella typhi is important for protective immunity against typhoid fever, as indicated by the protection obtained with killed cell vaccines and component vaccines (outer membrane proteins, Vi antigen) in animals and human beings. Nonetheless, analysis and interpretation of host humoral immune response to S. typhi surface antigens have been difficult because of the complex structure of the S. typhi envelope and the lack of purified reagents for detection of immune response to individual surface components. Normal and convalescent human sera from typhoid fever patients were absorbed with S. typhi lipopolysaccharide. These sera were used in radioimmunoprecipitation assays of whole S. typhi cells and S. typhi membranes labelled with either 125I or 35S-methionine. This strategy has permitted the unequivocal identification of a humoral immune response to structural and in vivo induced outer membrane proteins of S. typhi. In this manner, we have identified the porins, lipoprotein, the iron-starvation-induced proteins, and three proteins of 30, 18.5 and 15 kDa as surface-exposed immunogens of S. typhi in patients with typhoid fever. These studies suggest that further experimental work is needed to characterize the relevance of both anti-S. typhi outer membrane protein and antilipopolysaccharide antibodies in recovery from S. typhi infections and protective immunity.
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PMID:Lipopolysaccharide-independent radioimmunoprecipitation and identification of structural and in vivo induced immunogenic surface proteins of Salmonella typhi in typhoid fever. 842 32

Primary microglial cultures prepared from newborn mice showed the production and release of the third component of complement (C3). Newly synthesized [35S]methionine-labelled C3 was purified by immunoprecipitation using anti-C3-antibody. C3 was detected by SDS-PAGE and fluoroaraphy of the immunoprecipitated protein from cell lysates as a 195 kDa band, and from the supernatants of cultures as two major bands corresponding to the C3 alpha-chain (125 kDa) and beta-chain (75 kDa), consistent with known C3 characteristics. Increased biosynthesis of C3 was elicited by endotoxin lipopolysaccharide (LPS). Further, the synthesis of C3 was increased 5-10-fold in response to various synthetic peptides corresponding to the amyloid beta/A4 protein, which is the main constituent of extracellular amyloid deposits in Alzheimer's disease (AD). The increased synthesis of C3 was shown to be dose dependent at concentrations of beta/A4 peptide ranging from 10 micrograms/ml to 50 micrograms/ml. These results suggest that complement components found previously in amyloid deposits may be partly derived from reactive microglia preferentially associated with senile plaques in AD brain.
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PMID:Synthetic Alzheimer amyloid beta/A4 peptides enhance production of complement C3 component by cultured microglial cells. 843 89

Previous studies have demonstrated that endotoxin/lipopolysaccharide treatment causes a decrease in adipose tissue and heart lipoprotein lipase (LPL) activities in rats, producing hypertriglyceridemia in these animals. To examine the mechanisms for this effect of endotoxin, we studied the effects of endotoxin administration on LPL mRNA, and LPL synthetic rates and activity in rat adipose tissue and heart. Endotoxin treatment (i.p., 3 mg/100 g body weight or higher doses) produced a pronounced increase in serum triglycerides associated with a 65% decrease in adipose tissue and heart LPL activities within 7 h. Fast protein liquid chromatography (FPLC), used to separate lipoproteins in rat serum, showed that the increase in triglyceride was all in the very low density lipoprotein fraction which was accompanied by a concomitant decrease in high density lipoprotein. In contrast, there was no change in adipose tissue or heart LPL mRNA up to 24 h after treatment and no change in adipose tissue LPL synthetic rate, as measured by L-[35S]methionine incorporation and immunoprecipitation. Plasma insulin levels remained unchanged. The results indicate that endotoxin-induced hypertriglyceridemia in rats can be attributed to an impaired triglyceride clearance associated with a decrease of LPL activity mediated at a post-transcriptional level.
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PMID:Endotoxin-induced hypertriglyceridemia is mediated by suppression of lipoprotein lipase at a post-transcriptional level. 844 38

Interleukin-1 is a macrophage-derived cytokine, which can also be synthesized in other cell types. It has been shown to exert several activities in the nervous and endocrine system, including a potent activating effect on the hypothalamo-pituitary-adrenal axis. High levels of interleukin-1 have previously been found in the adrenal gland. The effect of bacterial lipopolysaccharides (2.0 mg/kg) on interleukin-1 beta mRNA was studied in the rat adrenal gland by in situ hybridization histochemistry using a synthetic oligonucleotide probe. A transient induction was observed, with the strongest hybridization signal seen after 1.5 h and subsequent decrease to near basal levels at 3 h. Similarly, the effect of lipopolysaccharides on preproenkephalin A mRNA expression in the adrenal gland was analyzed. Preproenkephalin A is a precursor for methionine-enkephalin, a neuropeptide known to be produced in the chromaffin cells, and also known to affect immunological functions. A low level of preproenkephalin A mRNA was seen in the adrenal medulla in animals injected with saline and 0.5 h after lipopolysaccharide administration. A small, but distinct increase in hybridization signal appeared at 1.5 h and a marked increased was observed at 3 h after administration of lipopolysaccharides. In addition to the different kinetics of expression after LPS administration, the two mRNA species showed a somewhat different morphological distribution in that IL-1 beta mRNA could be seen in both adrenal medulla and cortex, whereas preproenkephalin A expression was confined to the adrenal medulla.
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PMID:Induction of interleukin-1 beta mRNA and enkephalin mRNA in the rat adrenal gland by lipopolysaccharides studied by in situ hybridization histochemistry. 852 Nov 41

Substance P (SP) is an undecapeptide that has the amino sequence Arg-Pro-Lys-Pro-Gin-Gln-Phe-Phe-Gly-Leu-Met-NH2 and that belongs to a family of structurally related peptides known as tachykinins, the latter are widely distributed in the central nervous system. SP is involved in the biological activities of cells in the immune system, including the induction of cytokines in immune cells. We have investigated the effects of SP on constitutive and/or lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF) in cultured blood monocyte-derived macrophages (MDM). Cells cultured in vitro for 14 days were treated with SP at various concentrations (10(-10) to 10(-6M) in the presence of LPS before culture supernatants were harvested. TNF bioactivity in culture supernatants was measured with L929 cell line MDM from 10 of 12 donors treated with a SP alone showed increased TNF production. SP and LPS also interacted in a synergistic fashion in upregulating TNF production in MDM from responders. The stimulatory effect of SP was inhibited by two SP antagonists, spantide ([D-Arg-1-D-Trp-7-D-Trp-7-D-Trp-9-leu-11]-SP) and CP-96,345 (a nonpeptide antagonist of the SP receptor). In addition, an anti SP polyclonal antibody blocked the SP effect on TNF production in cultured MDM, further indicating the specificity of these effects. These results demonstrate that SP is an important regulator of monokine production by human monocytes/macrophages.
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PMID:Substance P augments tumor necrosis factor release in human monocyte-derived macrophages. 855 79

We hypothesized that adenosine, known to be release from inflammatory sites, could lessen the potentially damaging activity of neutrophils (PMN) primed by tumor necrosis factor-alpha (TNF alpha) at sites of infection. We investigated the effect of adenosine on PMN primed with cell-free medium from mononuclear leukocytes (MNL) that had been treated with lipopolysaccharide (LPS) yielding a conditioned medium rich in TNF alpha and on PMN primed with recombinant human TNF alpha (rhTNF alpha). LPS (10 ng/mL) minimally primed PMN, but LPS-MNL-conditioned medium increased PMN chemiluminescence in response to f-Met-Leu-Phe (fMLP) 1242% compared with unprimed PMN. LPS-MNL-conditioned medium contained adenosine (approximately 30 nM). Converting the adenosine in the LPS-MNL-conditioned medium to inosine with adenosine deaminase (ADA) or blocking adenosine binding to PMN with the adenosine receptor antagonist 1,3-dipropyl-8-(phenyl-p-acrylate)-xanthine (BW A1433U) resulted in a near doubling of chemiluminescence. The LPS-MNL-conditioned medium contained TNF alpha (836 pg/mL; approximately 1 U/mL). Recombinant human TNF alpha (1 U/mL) primed PMN for a 1033% increase in chemiluminescence. Added adenosine decreased rhTNF alpha-primed PMN chemiluminescence (IC50 approximately 100 nM), and adenosine (100 nM) decreased both superoxide and myeloperoxidase release from rhTNF alpha-primed fMLP-stimulated PMN. The activity of adenosine was counteracted by ADA and BW A1433U, and the modulating effect of adenosine was on the primed response rather than on priming per se. Thus, physiological concentrations of adenosine reduce the effects of recombinant human TNF alpha and native human TNF alpha (released from LPS-treated MNL) on PMN activity. Endogenous adenosine may preclude or minimize damage to infected tissue by damping the TNF alpha-primed PMN oxidative response.
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PMID:Adenosine modulation of tumor necrosis factor-alpha-induced neutrophil activation. 861 64

This study investigated the role of intracellular calcium concentration ([Ca]i) as a possible intermediate in the lipopolysaccharide (LPS) second messenger pathway for the activation of neutrophils (polymorphonuclear leukocytes [PMNs]). Isolated PMNs were loaded with the calcium-sensitive fluorescent dye fura-2. The PMNs were stimulated with either LPS or the positive control formyl-Met-Leu-Phe (fMLP). As expected, PMN exposure to fMLP increased [Ca]i. However, LPS stimulation did not induce any detectable changes. Depletion of intracellular Ca stores with thapsigargin, or extracellular Ca with EGTA, significantly inhibited the upregulation of the CD11b/CD18 integrin in response to fMLP but not LPS. We conclude that [Ca]i is not an early intermediate in the second-messenger pathway for the activation of PMNs by LPS.
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PMID:Role of calcium during lipopolysaccharide stimulation of neutrophils. 869 14

1. Engagement of adenosine A2 receptors suppresses several leukocyte functions. In the present study, we examined the effect of adenosine on the inhibition of leukotriene B4 (LTB4) synthesis in heparinized human whole blood, pretreated with lipopolysaccharide (LPS) and tumour necrosis factor alpha (TNF-alpha) and stimulated with the chemotactic peptide, N-formyl-Met-Leu-Phe (FMLP). 2. The FMLP-induced synthesis of LTB4 in whole blood pretreated with LPS and TNF-alpha was dose-dependently inhibited by adenosine analogues in the following order of potency; 5'(N-ethyl)carboxamidoadenosine (NECA) approximately equal to CGS 21680 > 2-Cl-adenosine > N6-cyclopentyladenosine (CPA), indicating the involvement of the adenosine A2 receptor subtype. The IC50 values for NECA, CGS 21680, 2-Cl-adenosine, and CPA were 6 nM, 9 nM, 180 nM, and 990 nM, respectively. 3. Dipyridamole, an agent that blocks the cellular uptake of adenosine by red cells and causes its accumulation in plasma, also inhibited the synthesis of LTB4 in LPS and TNF-alpha-treated whole blood stimulated by FMLP; moreover, this inhibition was reversed upon addition of adenosine deaminase. 4. A highly selective antagonist of the adenosine A2 receptor, 8-(3-chlorostyryl)caffeine (CSC), reversed the inhibition of LTB4 synthesis by 2-Cl-adenosine and dipyridamole in LPS and TNF-alpha-treated whole blood, stimulated by FMLP. 5. LTB4 synthesis in whole blood originates predominantly from neutrophils and to a lesser extent from monocytes. 2-Cl-adenosine also inhibited the synthesis of LTB4 induced by FMLP in these isolated LPS and TNF-alpha-treated cells; however, 2-Cl-adenosine was a more potent inhibitor of LTB4 synthesis in neutrophils than monocytes. 6. The present data demonstrate that adenosine, acting through A2 receptors, exerts a potent inhibitory effect on the synthesis of LTB4 and thus contribute to the understanding of its anti-inflammatory properties.
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PMID:Adenosine A2 receptor-induced inhibition of leukotriene B4 synthesis in whole blood ex vivo. 873 71


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