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)

Marked formation of N-nitrosothioproline (N-nitrosothiazolidine-4-carboxylic acid) by stimulation with Escherichia coli lipopolysaccharide (LPS) was demonstrated in ascorbic acid-deficient mutant rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amounts of urinary nitrate and N-nitrosothioproline excretion after thioproline administration was measured in ODS rats with and without ascorbic acid supplement before and after the injection of LPS. LPS caused marked increase of urinary nitrate excretion in both groups. Urinary N-nitrosothioproline excretion increased 6-fold after LPS injection in ODS rats not supplied with ascorbic acid, but supplement with ascorbic acid markedly decreased the excretion of N-nitrosothioproline.
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PMID:Marked nitrosation by stimulation with lipopolysaccharide in ascorbic acid-deficient rats. 220 2

The effect of ascorbic acid deficiency on the urinary excretion of nitrate was investigated using a mutant strain of rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amount of urinary nitrate excreted by ODS rats with or without ascorbic acid supplementation were measured before and after the intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). Urinary nitrate excretion increased markedly after LPS injection. Urinary nitrate excretion by ODS rats not supplied with ascorbic acid was significantly less than that of those supplied with ascorbic acid both before and after LPS injection. These results show that ascorbic acid enhances both LPS-stimulated and constitutive nitrate production in vivo.
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PMID:Decrease of nitrate biosynthesis in scorbutic mutant rats unable to synthesize ascorbic acid. 233 89

The osteoclast may be of hematopoietic lineage and as such its development could be regulated by colony-stimulating factors. Since there is much interest as to whether osteoblasts influence bone resorption, we examined whether bone cells produce colony-stimulating activity. Both cells isolated from neonatal calvaria and the osteogenic cell MC3T3-E1 were found to constitutively release a colony-stimulating activity possessing characteristics of a macrophage colony-stimulating factor, as determined by basic biochemical purification and by identity of colonies induced in cultures of bone marrow cells. Release could be increased by the presence of the bone-resorbing agents lipopolysaccharide and 1,25 dihydroxyvitamin D3. We conclude that the osteoblast may contribute to both the processes of osteoclast formation and of hematopoiesis through the secretion of colony-stimulating activity into the adjacent bone marrow.
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PMID:Murine osteoblastlike cells and the osteogenic cell MC3T3-E1 release a macrophage colony-stimulating activity in culture. 311 42

Urinary excretions of nitrate and N-nitrosothiazolidine-4-carboxylic acid (N-nitrosothioproline; NTPRO) were determined in rats with osteogenic disordered syndrome (ODS, od/od), lacking L-ascorbic acid (ASC) biosynthesis, after i.p. administration of Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) followed by thiazolidine-4-carboxylic acid (thioproline, 20 mg/rat). L-Ascorbic acid-sufficient ODS rats showed the excretion of nitrate and NTPRO at the levels of 20.3 +/- 7.9 mumol/24h and 369 +/- 111 pmol/24 h respectively, whereas the levels of nitrate and NTPRO in ASC-deficient (scorbutic) rats increased to 54.7 +/- 5.6 mumol/24 h (P < 0.01) and 796 +/- 367 pmol/24 h (P < 0.05) respectively. Administration of L-arginine further increased urinary excretion of nitrate and NTPRO while D-arginine showed no effect. NG-Monomethyl-L-arginine, a specific inhibitor of nitric oxide synthase (NOS), strongly inhibited endogenous formation of both nitrate and NTPRO. These results indicate that increased excretion of NTPRO in ODS rats stimulated by LPS involves induction of NOS leading to an increase in endogenous formation of reactive nitrogen oxides such as N2O3, a potent nitrosating agent at physiological pH conditions. Increased NOS activities in the plasma and various tissues of ODS rats were observed 5 h after treatment with LPS. The possibility of extragastric N-nitroso compound formation in inflammation sites is discussed.
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PMID:Marked increase in urinary excretion of nitrate and N-nitrosothioproline in the osteogenic disordered syndrome rats, lacking ascorbic acid biosynthesis, by administration of lipopolysaccharide and thioproline. 758 82

By using an in vitro bone-forming culture system, the chick periosteal osteogenesis (CPO) model, the direct effects on osteogenesis of sonicated extracts derived from oral bacteria were examined. Both extracts from bacterial species having strong associations with periodontal diseases (Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Prevotella intermedia, hereinafter referred to as suspected periodontopathogens) and extracts from species not correlated with periodontal disease (Streptococcus sanguis, Veillonella atypica, and Prevotella denticola, hereinafter referred to as nonpathogenic bacteria) were tested. All bacterial cultures were grown under standard anaerobic culture conditions. Sonicated bacterial extracts were prepared from the bacterial pellet. These were added in various proportions to the CPO cultures. Parameters of osteogenesis, including alkaline phosphatase activity, calcium and P(i) accumulation, and collagen synthesis, were measured in 6-day-old cultures. Compared with controls grown in the absence of bacterial products, osteogenesis was inhibited significantly in cultures treated with extracts derived from the suspected periodontopathogens. No osteogenic inhibition was observed in cultures treated with extracts from the nonpathogenic bacteria. These results suggest that the ability to inhibit osteogenesis in vitro may be a pathogenic property shared by a limited group of species. Further characterization of the P. gingivalis extracts revealed that both proteinaceous and nonproteinaceous products, including lipopolysaccharide, were able to inhibit osteogenesis. P. gingivalis extract-mediated inhibition of osteogenesis in CPO cultures was blocked by indomethacin, implicating prostaglandins in the regulation of the bacterial effects. The bacterial extracts had either reversible or irreversible inhibitory effects on osteogenesis when added after differentiation or before/during differentiation of bone cells, respectively.
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PMID:Characterization of inhibitory effects of suspected periodontopathogens on osteogenesis in vitro. 764 57

MC3T3-E1 mouse clonal osteogenic cells were incubated with interferon-gamma, interleukin-1 beta, tumor necrosis factor-alpha, and E. coli lipopolysaccharide. TNF alpha, IL-1 beta, and LPS caused a dose- and time-dependent increase of nitrite (NO2-), the stable metabolite of nitric oxide (NO), in conditioned media over 48 hours, while IFN gamma had a minimal effect. Different combinations of the same factors caused a synergistic enhancement of NO2- accumulation, except for IL-1 beta with LPS. The earliest detectable NO2- production was at 6-9 hours, with continued accumulation over 48 hours. NO2- production was inhibited dose-dependently by three arginine analogs known to be specific inhibitors of NO synthase, as well as by actinomycin D, cycloheximide, and dexamethasone; EGTA or indomethacin had a small inhibitory effect. It is concluded that osteoblast-like cells can be induced by proinflammatory cytokines and bacterial endotoxin to produce NO, which can play an important role in bone pathophysiology.
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PMID:Cytokines induce nitric oxide production in mouse osteoblasts. 800 32

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor with a regulatory effect on the transformation of immature macrophages into multinucleated giant cells (MNGC) that exhibit phenotypic and functional characteristics of osteoclasts (OC). The authors analyzed the bone implant interface membranes harvested from 15 patients with failed total joint replacements for the production and tissue distribution of GM-CSF and interleukin-1 (IL-1). Immunohistology and liquid culture were employed to assess the contribution of these factors in the recruitment of macrophages and the development of bone resorbing MNGC at these sites. This process has been implicated in osteoclastic bone resorption, bone, and bone marrow necrosis adjacent to orthopaedic implants. Histologic assessment of the interface indicated the presence of granuloma and a variable number of MNGC in 11 cases. Four cases showed sites of intramembranous formation of osteoid and mineralized bone that was accompanied by normal bone marrow in two cases. Granulocyte-macrophage colony stimulating factor was expressed by a distinct subset of phagocytic macrophages in the lining layer on the implant side. interleukin-1-positive cells outnumbered those stained for GM-CSF. Stimulation of cultured cells with prosthetic metal particulate material showed marked similarity in the expression of these cytokines to cultures treated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA). The induction of GM-CSF production in the lining layer where small MNGC develop indicates that these cells differentiate locally following the phagocytosis of particulate wear debris. In conclusion, GM-CSF promotes the proliferation and early stages of fusion and development of MNGC responsible for osteolysis at these sites. These results also highlight the capacity of the interface to display both osteogenic and inflammatory characteristics. Collectively, the findings suggest that the local bone marrow could participate in the development of the interface as a source of myeloid cells in addition to the capacity of marrow stroma to generate various osteogenic cells essential for the ingrowth of bone into prosthetic implants.
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PMID:Assessment of the role of GM-CSF in the cellular transformation and the development of erosive lesions around orthopaedic implants. 862 73

Recombinant human BMP-7 (bone morphogenetic protein-7, osteogenic protein-1) is osteogenic, dentinogenic and cementogenic when implanted into the appropriate tissue in vivo. However, most studies characterizing the induction of these tissues have implanted BMP-7 into freshly surgerized, clinically healthy tissues. To determine if BMP-7 is dentinogenic in inflamed dental pulps, we applied BMP-7 to inflamed ferret pulps. A single application of 5 microg of a commercial preparation of lipopolysaccharide (LPS) from Salmonella typhimurium directly to the coronal pulp induced a reversible mixed inflammatory exudate of moderate intensity within 3 d. Treatment with a single application of 2.5, 7.5 or 25 microg recombinant human BMP-7/mg collagen (2 mg total mass/tooth) induced reparative dentinogenesis in controls but not LPS treated dental pulps. These data reveal that a single application of up to 50 microg/tooth of exogenous recombinant BMP-7 is insufficient to induce reparative dentinogenesis in ferret teeth with reversible pulpitis. Given that pulp cells in the inflamed tissues likely retain the capacity to respond to exogenous BMP-7, it is possible that insufficient active recombinant protein is available to induce tissue formation in experimentally inflamed dental pulps.
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PMID:Treatment of inflamed ferret dental pulps with recombinant bone morphogenetic protein-7. 1087 90

Leptin, the product of the ob gene, regulates food intake, energy expenditure, and other physiological functions of the peripheral tissues. Leptin receptors have been identified in the hypothalamus and in extrahypothalamic tissues. Increased circulating leptin levels have been correlated with cardiovascular disease, obesity, aging, infection with bacterial lipopolysaccharide, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-related vascular disease. In addition, the differentiation of marrow osteoprogenitor cells is regulated by leptin. Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested the effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro. When treated with leptin, these calcifying vascular cells had a significant 5- to 10-fold increase in alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells. Prolonged treatment with leptin enhanced the calcification of these cells, further supporting the pro-osteogenic differentiation effects of leptin. Furthermore, the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial cells, and the expression of leptin by artery wall cells and atherosclerotic lesions in mice. Taken together, these results suggest that leptin regulates the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.
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PMID:Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. 1134 6

Adult mesenchymal stem cells (MSCs) are promising tools for such applications as tissue engineering and cellular therapy. It is not clear how stem cells exposed to unfavorable conditions (e.g., hypoxia or inflammation) respond to signals of danger after in vivo transplantation. Toll-like receptors (TLRs) play a major role in the immune system, participating in the initial recognition of microbial pathogens and pathogen-associated components. This study was designated to determine the role of TLRs in human MSCs. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry analysis demonstrated that MSCs derived from human adipose tissue and bone marrow express TLR-1, TLR-2, TLR-3, TLR-4, TLR-5, TLR-6, and TLR-9. We investigated induction of the differentiation and proliferation of human adipose tissue stromal cells (hADSCs) by TLR agonists, including flagellin, peptidoglycans (PGN), lipopolysaccharide (LPS), the synthetic double-stranded RNA analog poly(I:C), and synthetic CpG oligodeoxydinucleotide (CpG-ODN). None of these agonists, except ODN, affected the proliferation of hADSCs. LPS and PGN increased osteogenic differentiation, but CpG-ODN decreased it. Poly(I:C) itself did not affect adipogenic or osteogenic differentiations, but exerted a synergistic effect on LPS- or PGN-induced osteogenic differentiation. RT-PCR analysis demonstrated that LPS and PGN induce osteogenic markers in hADSCs. TLR agonists affected the expression of chemokines and cytokines differentially. Furthermore, hADSCs affected the expression of specific TLRs in vitro under hypoxic conditions. These data provide evidence of a nonimmune role for TLR signaling on MSCs and may provide clues to the behavior of transplanted MSCs in vivo.
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PMID:Role of toll-like receptors on human adipose-derived stromal cells. 1690 95


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