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)

The effect of running activity on normal and inflamed knees was determined by light microscopic (LM) and scanning electron microscopic (SEM) observations on hamster articular cartilage. Animals were split into two groups; one housed in standard cages and one given free access to running wheels. Twenty-one days prior to analysis, half of each group was given an intra-articular injection of lipopolysaccharide (LPS) to cause an inflammation, the other half were uninjected. No remarkable changes were observed by LM in either the control running or nonrunning groups. In contrast, cartilage proteoglycan depletion, and pannus and synovial hyperplasia were equally observed in both groups of LPS-injected animals. SEM observations on the patellae from control animals found them to be free from damage to the articular cartilage. The joints of both the LPS nonrunning and running animals contained synovial hypertrophy with villus projection from the synovial lining. However, only the LPS-injected running hamsters had cartilage fraying over large areas of the articular surface, as well as areas in which the villus projections had been flattened. These results demonstrated that mechanical stress applied to a proteoglycan-depleted cartilage enhances the breakdown of the collagen matrix as judged by fibrillation, and may aggravate the inflammation by crushing the swollen synovial lining where it encroaches on the joint space.
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PMID:Effects of exercise on synovium and cartilage from normal and inflamed knees. 772 94

Studies were performed to evaluate the effect of several factors on the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages. In vivo apoB-lipoprotein-proteoglycan complex was isolated from human aorta fibrous-plaque lesions and low-density lipoprotein (LDL)-proteoglycan complex was formed in vitro. Degradation of LDL-proteoglycan complex and cholesteryl ester synthesis mediated by the in vivo and in vitro complexes were lowest in freshly isolated monocytes. With the maturation of monocytes into macrophages, there was a dramatic rise in both. The degradation of the complex and the resultant stimulation of cholesterol esterification increased significantly with increasing cell density. Preincubation of macrophages in medium containing lipoprotein cholesterol did not down-regulate the subsequent degradation of LDL-proteoglycan complex. Macrophage-conditioned medium had a profound stimulatory effect on the degradation of LDL-proteoglycan complex and cholesterol esterification by mature macrophages and freshly isolated monocytes. The conditioned medium lost its stimulatory activity after boiling, dialysis and trypsin digestion. Macrophage activation with phorbol ester and bacterial lipopolysaccharide resulted in a marked suppression of the binding and degradation of the complex, as well as the complex-mediated cholesteryl ester synthesis. These results demonstrate that several factors regulate the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages.
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PMID:Regulation of the metabolism of lipoprotein-proteoglycan complexes in human monocyte-derived macrophages. 805 93

Arthritis refers to a heterogeneous class of diseases characterized by impairment of movement. Yet animal models of arthritis have traditionally been based on the utilization of animals housed without the capability of extended free movement and without adjunctive measurement of mobility. To define the determinants of mobility impairment, we have established a lipopolysaccharide (LPS)-induced arthritis model in the hamster that prominently features monitoring of mobility and compares mobility changes with histological and biochemical changes during arthritis. Intraarticular LPS induces a dose-dependent inhibition of the hamster's mobility as measured by decreased daily distance on a running wheel (normal distance 9 to 12 km/day). At low concentrations of LPS (0.1 and 1 microgram/knee), daily distances returned to normal after 4 and 6 days, respectively. At higher concentrations, the mobility was still markedly suppressed after 6 days, and, at 100 micrograms/knee, irreversible chondrocyte loss was observed on the femoral condylar margins. Further studies were therefore conducted using 1 microgram LPS/knee. Histological and biochemical changes were examined to determine which resolved at the time of restoration of mobility. At the time of restoration of mobility, the synovial capsule was still edematous and heavily infiltrated with leukocytes; proteoglycan loss from the medial femoral condyle was still increasing. Plasma keratan sulfate failed to correlate with either proteoglycan loss or mobility changes. Proteoglycan synthesis, which was maximally suppressed the second day after LPS, was enhanced over controls at the time of restoration of mobility, suggesting the onset of repair. These results suggest a possible association of mobility inhibition with local cytokine synthesis. This model provides an approach to define the causes of mobility impairment.
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PMID:Comparison of mobility changes with histological and biochemical changes during lipopolysaccharide-induced arthritis in the hamster. 817 33

To study proteoglycan metabolism in inflammatory macrophages, primary cultures of human macrophages were cultured in the absence and presence of bacterial lipopolysaccharide (LPS). When exposed to [35S]sulfate, the cells incorporated the label almost exclusively into chondroitin sulfate proteoglycan (CSPG), which was recovered from the culture medium and the cell layer. Cells stimulated with LPS secreted approximately three times more [35]CSPG into the culture medium than control cells. Furthermore, cell adhesion was also found to promote proteoglycan secretion; when nonadherent monocytic cells were induced to adhere, the release of proteoglycan increased two times. The increased secretion seen in LPS-stimulated macrophages was partly due to increased biosynthesis, but was mostly due to increased sorting of CSPG to the secretory pathway. Only about 20% of the CSPG synthesized in unstimulated cells was secreted, whereas the corresponding figure in LPS-treated cells was 35%. In both cell types, the remaining [35S]CSPG was degraded, probably in the lysosomes. The degradation was a two-step process. First, the [35S]CSPG was rapidly cleaved to yield free glycosaminoglycan (GAG) chains (t1/2 = 15 to 30 minutes). Secondly, the GAG chains were completely depolymerized (t1/2 = 2 to 3 hours). Neither resting nor LPS-stimulated cells sorted CSPG to intracellular storage, as is evident in many hematopoietic cells. The LPS-treated cells synthesized [35S]CSPG of smaller molecular size than did control cells, with GAG chains of approximate molecular mass of 12 kD versus 16 kD in control cells. No difference was seen in the disaccharide composition of the GAG chains; both LPS-stimulated and unstimulated cells expressed a mixture of 80% to 90% chondroitin 4-sulfate and 10% to 20% chondroitin 4,6-disulfate. N-terminal sequence and Northern blot analysis indicate that the core protein of the CSPG secreted by human macrophages is serglycin.
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PMID:Proteoglycan metabolism in normal and inflammatory human macrophages. 821 36

Injection of lipopolysaccharide (LPS) into rabbit knee joints provoked leucocyte infiltration and loss of proteoglycan (PG) from the cartilage. We investigated the role of IL-1 and IL-1 receptor antagonist (IL-1Ra) and its significance in the pathogenesis of LPS-arthritis. Production of IL-1 beta peaked at 6 h (196.7 +/- 89.4 pg/joint) after injection of 10 ng of LPS, while IL-1Ra peaked at 9 h (34.5 +/- 13.4 ng/joint). The amount of IL-1Ra was 180-200-fold molar excess of IL-1, and a large amount of IL-1Ra was sustained for 1 week. Both IL-1 beta and IL-1Ra were mainly produced by synovial exudate cells. Arthritis was reproduced by rabbit IL-1 beta. LPS-induced leucocyte infiltration was inhibited 70-75% by rabbit IL-1Ra. Loss of PG in LPS-arthritis was prevented by IL-1Ra and also by neutrophil elastase inhibitor, and superoxide dismutase. In leucopenic rabbits, injection of LPS induced neither production of IL-1 beta nor loss of PG. Direct injection of inflammatory exudated cells in leucopenic rabbits reproduced loss of PG, and there was only a partial recovery by IL-1Ra. These results suggest that LPS-initiated IL-1 acts as a key mediator in LPS-arthritis and that endogenous IL-1Ra may suppress a part of IL-1 activity at the site, but its amount was too low for suppression of the produced IL-1. Loss of PG is a sequela of infiltrated leucocytes and leucocyte-derived elastase, and superoxide anion may play a pivotal role in the destruction of cartilage.
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PMID:Production of IL-1 and IL-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits. 834 45

Chronic inflammation and degradation of connective tissue in the course of periodontitis are maintained by bacterial products such as lipopolysaccharides (LPS), which probably act via inflammation mediators, e.g. cytokines. We investigated the effects of lipopolysaccharide (LPS) from E. coli and mouse recombinant interleukin 1 alpha (mrIL-1) on chondrogenesis, endochondral mineralization, matrix metalloproteinase activation and matrix degradation in vitro using cartilage organoid cultures. Mesenchymal cells of limb buds from mouse embryos (day 12) were grown at high density on a membrane filter at the medium/air interphase for 14 days. Chondrogenesis occurred during the first 6 days of culture. Endochondral mineralization took place upon addition of 5 mM beta-glycerophosphate from day 7 to 14. Treatment of the cultures with LPS and mrIL-1 on days 2 to 14 and during mineralization on days 7 to 14 resulted in a marked decrease of types I and II collagen, matrix mineralization and proteoglycan content. In the medium, proteoglycan content and metalloproteinase activity were enhanced. LPS induced IL-1 alpha production and release into the medium. LPS antagonist polymyxin B partly abolished the LPS effect, whereas IL-1 receptor antagonist (IL-1ra) partly abolished both LPS and mrIL-1 effects. Reversal of LPS-induced effects by IL-1ra was comparable to the reversal of mrIL-1 effects, only the decrease in type II collagen after LPS treatment was abolished to a lesser extent by IL-1ra.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of metalloproteinase activity, cartilage matrix degradation and inhibition of endochondral mineralization in vitro by E. coli lipopolysaccharide is mediated by interleukin 1 alpha. 858 63

In this study, we examined the influence of lipopolysaccharide (LPS) on aggrecan metabolism and structure in the growth plate. Two experimental approaches were used: (i) in vivo administration of LPS to 10-day-old chicks; and (ii) in vitro addition of LPS to explant culture of normal chick growth plate. Twelve-day-old male broiler chicks were killed 48 hr after intravenous injection of LPS (3 mg/kg) or saline (control), and growth plate from the femur or tibia was cultured or frozen. Tissue for explant culture was (i) cultured for 5 days with daily medium change (glycosaminoglycan release into the medium estimates proteoglycan breakdown rates), or (b) incubated with 35SO4 to determine the rate of proteoglycan synthesis. Proteoglycan structure was determined by associative (0.5 M sodium acetate) and dissociative (4 M guanidine HCl) Sepharose CL2B chromatography. Explant culture of growth plate from LPS-injected chicks (in vivo) showed a decrease (P < 0.05) in the rate of proteoglycan synthesis. There were a greater proportion of small monomers and a reduced ability to aggregate in growth plate from LPS-injected chicks. In vitro addition of LPS (100 micrograms/ml) to explant culture medium reduced proteoglycan synthesis (P < 0.02), and the rate of release was increased (P < 0.001). In addition, the total and newly synthesized proteoglycans released into the medium from LPS-treated explant culture had a reduced aggregation and a majority of monomers that were smaller than control. These results demonstrate that LPS disrupts the normal metabolism and structure of growth plate aggrecan, and we hypothesize that this may adversely influence longitudinal growth.
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PMID:Lipopolysaccharide alters aggrecan metabolism in the growth plate. 875 97

The effects of inflammation on the biochemical and biomechanical properties of articular cartilage at two sites (dorsal and palmar) from the radial facet of the equine third carpal bone were examined in response to a synovitis induced with Escherichia coli lipopolysaccharide (LPS). Four groups were studied. In group 1 synovitis was induced at time zero and evaluated at week 6. Group 2 was the sham-treated control for group 1. In group 3 synovitis was induced at time zero and evaluated at week 2. Group 4 was the sham-treated control for group 3. There was a significant increase (P < 0.05) in newly synthesized proteoglycan PG from both sites in group 3 as compared to the sham-treated groups and group 1. No significant difference in the endogenous PG concentration between groups or sites was detected. Sepharose CL-2B revealed two peaks of newly synthesized PG in all groups; an early peak (Kav 0.11-0.13) and a late peak (Kav 0.48-0.64). Newly synthesized PG profiles from sham-treated groups and group 3 were similar, but the group 3 PG profile exhibited a more pronounced early peak. Conversely, the PG profile from group 1 demonstrated a more prominent late peak. Electrophoresis and Western blot analysis of the pooled late PG peak fractions from the sham-treated and group 1 showed a single toluidine blue stained band from both sites which reacted with monoclonal antibody (MAb) 1C6. By contrast, the late peak from the palmar site in group 3 showed an additional faster moving component on composite gels which did not react with MAb 1C6. There was a significant decrease in Poisson's ratio and a significant increase in cartilage thickness in groups 1 and 3 which had received synovitis. The increase in cartilage thickness of groups 1 and 3 was also significantly affected by site (dorsal > palmar). There was no significant difference in aggregate modulus or permeability constant among groups. Primary joint inflammation induced by LPS alters the biochemical and biomechanical properties of the articular cartilage as a function of time and site. An increase in chondrocyte PG synthesis in the early period following synovitis may be a reparative response to the inflammatory insult. Continued alterations in the qualitative PG composition in the later period following synovitis may represent a shift in chondrocyte metabolism to repopulate the existing cartilage matrix.
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PMID:Biochemical and biomechanical alterations in equine articular cartilage following an experimentally-induced synovitis. 880 14

In neurodegenerative disease or after brain injury, parenchymal cells in the central nervous system are activated to produce inflammatory mediators, mainly consisting of cytokine-induced factors, in a manner similar to, but clearly different from a peripheral inflammatory response. The upregulated expression of several extracellular matrix proteins in astrocytes located surrounding a neuritic plaque in Alzheimer's disease is a good example of such a response. A family of mediators which is cytokine-induced during an inflammatory response in the periphery are the matrix metalloproteinases. Matrix metalloproteinases are calcium-requiring, zinc-containing endopeptidases that constitute a major component of the enzyme cascade responsible for degradation of extracellular matrix proteins such as collagen, proteoglycan and laminin. Little is known about the cellular source or the function of matrix metalloproteinases in the central nervous system or how their expression is regulated in brain. Thus, it was of interest to determine which factors of the so-called 'brain inflammatory response' regulate the expression of these proteases in the nervous system. To this end, we measured the expression of matrix metalloproteinases in cultured rat astrocytes and microglia after treatment with various cytokines. Interleukin-1 beta, tumor necrosis factor-alpha and lipopolysaccharide were potent stimulators of matrix metalloproteinase-2 (gelatinase A) and matrix metalloproteinase-9 (gelatinase B) in cultured rat astrocytes; the effect of each secretagogue was inhibited in the presence of glucocorticoid. Interleukin-1 beta and lipopolysaccharide also stimulated the production of matrix metalloproteinase-3 (stromelysin-1) in astrocytes. In addition, activated microglia release matrix metalloproteinase-9. The 'coactivator' of monocytic phagocytes, interferon-gamma, rather than augmenting the response to lipopolysaccharide, inhibited it. Thus, cytokines appear to be potent regulators of matrix metalloproteinase production in astrocytes and microglia. The presence of these enzymes in 'inflamed' central nervous system may suggest their involvement in the pathogenesis or progression of neurodegenerative diseases which are associated with an inflammatory component. Much remains to be learned about the potential substrates for these enzymes and the mechanism of their activation in the central nervous system.
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PMID:Regulation of matrix metalloproteinase expressions in astrocytes, microglia and neurons. 894 20

Neisseria meningitidis possesses a repertoire of surface adhesins that promote bacterial adherence to and entry into mammalian cells. Here, we have identified heparan sulphate proteoglycans as epithelial cell receptors for the meningococcal Opc invasin. Binding studies with radiolabelled heparin and heparin affinity chromatography demonstrated that Opc is a heparin binding protein. Subsequent binding experiments with purified 35SO4-labelled epithelial cell proteoglycan receptors and infection assays with epithelial cells that had been treated with heparitinase to remove glycosaminoglycans confirmed that Opc-expressing meningococci exploit host cell-surface proteoglycans to gain access to the epithelial cell interior. Unexpectedly, Opa28-producing meningococci lacking Opc also bound proteoglycans. These bacteria also bound CEA receptors in contrast to the Opc-expressing phenotype, suggesting that Opa28 may possess domains with specificity for different receptors. Opa/Opc-negative meningococci did not bind either proteoglycan or CEA receptors. Using a set of genetically defined mutants with different lipopolysaccharide (LPS) and capsular phenotype, we were able to demonstrate that surface sialic acids interfere with the Opc-proteoglycan receptor interaction. This effect may provide the molecular basis for the reported modulatory effect of capsule and LPS on meningococcal adherence to and entry into various cell types.
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PMID:Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors. 957 Apr 5


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