Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonencapsulated smooth strain of Klebsiella pneumoniae (Kp-MPG) on the oxidative burst of human blood monocytes was assessed by luminol-enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34-kd acylpoly(1,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC-APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp-MPG, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and a polymer of the latter compound, APG pol. EFA-APG directly stimulated monocyte CL, whereas Kp-MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA-APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA-APG. The stimulating action of EFA-APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti-Mac-1 directed against CD11b, the alpha chain of complement receptor type 3 (CR3; CD11b/CD18), strongly inhibited CL activation by EFA-APG and to a lesser extent CL activation by unopsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CD11b/CD18 integrin in the functional interaction of EFA-APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA-APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety.
 ...
PMID:Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Klebsiella pneumoniae. 143 64

Drug-induced gingival overgrowth is an adverse side effect associated principally with 3 different types of drugs; specifically the antiepileptic phenytoin, the calcium channel antagonist nifedipine, and the immunosuppressant cyclosporin. The present study has analyzed the effect of cyclosporin and lipopolysaccharide on fibroblasts from 3 different sources: 1) normal healthy human gingiva (NHGF); 2) overgrown gingiva from 2 patients taking cyclosporin (CHGF); and 3) human fetal lung (WI-38). Fibroblasts isolated from cyclosporin-associated gingival overgrowth were significantly less responsive to cyclosporin in terms of DNA, total protein, and proteoglycan synthesis. This finding supports the in vivo response where few fibroblasts are seen but marked overgrowth of fibrous tissue occurs. Lipopolysaccharide derived from Fusobacterium nucleatum and Escherichia coli was capable of inhibiting DNA synthesis significantly in all 3 fibroblast types. Total protein synthesis by CHGF cells was inhibited differentially by Fusobacterium nucleatum LPS and addition of cyclosporin to this system resulted in reversal of the inhibition. A synergistic effect was noted when the proteoglycan output of NHGF cells was assessed in response to co-incubation with cyclosporin and Escherichia coli LPS. The study shows that bacterial LPS may be an important co-factor in the pathogenesis of cyclosporin-induced gingival overgrowth.
 ...
PMID:The effect of cyclosporin and lipopolysaccharide on fibroblasts: implications for cyclosporin-induced gingival overgrowth. 152 83

The binding of a 34-kDa (mol. wt.) acylpoly(1,3)galactoside (APG) extracted from a membrane proteoglycan of Klebsiella pneumoniae to human blood leucocytes was investigated. APG is made of a long poly(1,3)galactose chain, a core-like region and a lipid moiety which comprises two glucosamine residues bound to a phosphate group and two beta OH myristic acids. Fluoresceinated APG was shown to bind preferentially to monocytes and to a lesser extent to polymorphonuclear neutrophils, as determined by flow cytometry. Binding of fluoresceinated APG was inhibited by unlabelled APG; it was concentration dependent, but not saturable, with rapid kinetics. It occurred at +4 degrees C but was markedly increased at 37 degrees C. It involved trypsin-sensitive molecules on the membrane of monocytes. Neither the parent proteoglycan nor lipopolysaccharide from K. pneumoniae or Salmonella minnesota competed for APG binding. A minor non-specific binding to lymphocytes, occurring predominantly on B cells, was observed. Unlike that of lipopolysaccharide, the APG binding was not blocked by polymyxin B sulphate. Interaction between the galactose chain of APG and the galactose receptor does not account for the binding of APG to monocytes because the galactose receptor (Mac-2) is expressed at high density on activated macrophages but not on monocytes. Despite its strong binding to human blood monocytes, APG displayed a much weaker activity than K. pneumoniae membrane proteoglycan with respect to induction of monocyte cytokine synthesis. When administered as a Technetium 99 conjugate, APG was shown to label inflammatory foci in experimental animals, and its property as a marker of macrophages is currently being evaluated in clinical trials.
 ...
PMID:Binding of a bacterial acylpoly(1,3)galactoside to human blood leucocytes. 161 80

The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp-MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives.
 ...
PMID:Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae. 162 18

Production of extracellular matrix proteins-in particular, the proteoglycans-by macrophages is important in many of their functions, including cell-cell recognition, adhesion and phagocytosis. In this study, we characterized changes in sulfated proteoglycan production by hepatic macrophages following in vivo activation with lipopolysaccharide. We found that both resident Kupffer cells and liver macrophages from lipopolysaccharide-treated rats incorporated [35S]sulfate into proteoglycans. Lipopolysaccharide-activated macrophages incorporated two to three times more of the label than did resident Kupffer cells. In addition, although both cell types produced chondroitin sulfate and heparan sulfate, resident Kupffer cells synthesized more chondroitin sulfate whereas lipopolysaccharide-activated cells produced more heparan sulfate. Using specific antibodies and flow cytometry, we also found that hepatic macrophages produced chondroitin-4-sulfate, chondroitin-6-sulfate and chondroitin-O-sulfate. Lipopolysaccharide-activated macrophages contained more chondroitin-4-sulfate and chondroitin-O-sulfate and less heparan sulfate than did resident Kupffer cells. Both tunicamycin and beta-D-xylosides, inhibitors of sulfated proteoglycan biosynthesis, were found to block phagocytosis by the cells. Taken together, these results suggest that sulfated proteoglycans are important in activation and functional responsiveness of liver macrophages.
 ...
PMID:Changes in sulfated proteoglycan production after activation of rat liver macrophages. 186 Jun 87

We investigated the effects of the beta-adrenoceptor agonist isoproterenol (ISO) and the alpha- and beta-adrenoceptor agonist norepinephrine (NE) on murine B-cell activation. Cells were stimulated either by anti-mouse mu-chain antibodies (anti-mu), or by lipopolysaccharide (LPS), or a membrane proteoglycan of Klebsiella pneumoniae (Kp MPG), a T-independent polyclonal activator distinct from LPS, which induces B-cell proliferation and Ig synthesis. ISO and NE enhanced LPS- and Kp MPG-induced B-cell proliferation and maturation into IgM-, IgG- and IgA-secreting cells. The enhancement was prevented by prior addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Earlier events in the LPS- and Kp MPG-stimulated B-cell activation, such as increases in Ia antigen expression and RNA synthesis, were not modified by the catecholamines. Unlike ISO and NE, the membrane-permeant cyclic adenosine 3',5'-monophosphate (cAMP) analogue dibutyryl cAMP (dbcAMP), and the potent adenylate cyclase activator forskolin did not enhance but even inhibited DNA synthesis and Ig secretion stimulated by LPS and Kp MPG. In addition, ISO and NE did not enhance but strongly inhibited anti-mu-induced B-cell proliferation, and these effects were mimicked by dbcAMP and forskolin. Collectively, the data demonstrate that beta-agonists differently modulate B-cell activation depending upon the polyclonal activator, and provide additional evidence for distinct biochemical mechanisms of B-cell activation by anti-mu and LPS. Moreover, our results indicate that beta-adrenergic stimulation up-regulates B-cell responses to LPS and Kp MPG by a novel and cAMP-independent pathway.
 ...
PMID:Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens. 215 73

Muramyl dipeptide, an essential structure for the diverse biologic activities of bacterial cell wall peptidoglycan, inhibited the synthesis of glycosaminoglycan/proteoglycan in cultured rabbit costal chondrocytes in a dose-dependent manner. Muramyl dipeptide, as well as lipopolysaccharide and interleukin-1 alpha, also enhanced the release of 35S-sulfate-prelabeled glycosaminoglycan/proteoglycan from the cell layer, which seems to reflect, at least partially, the increasing degradation of glycosaminoglycan/proteoglycan. Five synthetic analogs of muramyl dipeptide known to be adjuvant active or adjuvant inactive were tested for their potential to inhibit synthesis of glycosaminoglycan/proteoglycan and to enhance the release of glycosaminoglycan/proteoglycan in chondrocytes. The structural dependence of these synthetic analogs on chondrocytes was found to parallel that of immunoadjuvant activity. These results suggest that muramyl dipeptide is a potent mediator of catabolism in chondrocytes.
 ...
PMID:Catabolic effects of muramyl dipeptide on rabbit chondrocytes. 226 Oct 2

The long term (18 day) metabolic response of bovine articular cartilage to treatment with either E. Coli lipopolysaccharide (LPS) or interleukin 1 was studied. For LPS treatment, incorporation of [35S]sulfate into the large proteoglycan population was inhibited 80% while that into the small interstitial proteoglycans was only inhibited 40%. Incorporation of [3H]serine into the large proteoglycan population was inhibited approximately 72% while incorporation into other protein was inhibited only 16%. Furthermore, the rate of catabolism of [3H]serine labeled proteoglycans was increased 2-fold by LPS treatment while the rate of 3H-labeled general protein catabolism was not affected. Incorporation of [3H]glucosamine into hyaluronate was increased; however a correction for changes in the specific activity of the intracellular [3H]glucosamine precursor pool in LPS-treated cultures indicated that the net amount of hyaluronate synthesized was not altered by LPS treatment. The 3H/35S ratios in isolated chondroitin sulfate disaccharides labeled with [35S]sulfate and [3H]glucosamine precursors were significantly changed during long term LPS treatment, suggesting that general carbohydrate pathways are altered. The 3H/35S changes were larger in the disaccharides isolated from the small proteoglycans indicating that different precursor pools, probably in different cell populations, preferentially synthesize this proteoglycan population. Interleukin-1 affected the same chondrocytic pathways as LPS as shown by a) the extent of inhibition of proteoglycan synthesis, b) the selective inhibition of synthesis of the large proteoglycan species, c) acceleration of proteoglycan catabolism, d) net depletion of proteoglycans from the tissue, e) increases in guanidine HCl extractable [3H]hyaluronate, f) increases in levels of prostaglandin E2 synthesis, g) changes in 3H/35S ratios in glycosaminoglycan chains and, h) minimal effects on general protein synthesis.
 ...
PMID:Effects of interleukin-1 and lipopolysaccharides on protein and carbohydrate metabolism in bovine articular cartilage organ cultures. 250 33

Gingival overgrowth is an adverse side-effect seen in a proportion of patients taking cyclosporin-A which indicates that cyclosporine-A may modulate the activities of cells other than T lymphocytes. Therefore, the effect of cyclosporine on human gingival fibroblasts has been studied in vitro. Cyclosporine-A was found to stimulate DNA synthesis and the proliferative activity of these cells with maximal stimulation noted at a concentration of 10(-9) g/ml. Although this stimulation was most noticeable in the presence of 10% fetal calf serum, proliferation still occurred in serum-free medium. In the presence of lipopolysaccharide, at a concentration which normally inhibits gingival fibroblast proliferation, cyclosporine retained its capacity to stimulate proliferative activity. Fibroblasts isolated from overgrown gingival tissue responded to a greater extent than those isolated from a healthy site from the same individual. This stimulatory effect was not restricted to gingival fibroblasts, since human foreskin fibroblasts responded in a similar fashion. Cyclosporine-A did not significantly alter protein or proteoglycan production by these cells. These responses are considered to reflect the in vivo response of gingival overgrowth in patients taking cyclosporine-A. The reversal of lipopolysaccharide inhibition of gingival fibroblast proliferation by cyclosporine-A may explain, in part, why gingival overgrowth is most prominent in areas of heavy dental plaque accumulation.
 ...
PMID:Regulation of human gingival fibroblast growth and synthetic activity by cyclosporine-A in vitro. 253 56

Proteoglycan biosynthesis was studied in human monocytes and monocyte-derived macrophages (MDM) after exposure to typical activators of the monocyte/macrophage system: interferon-gamma (IFN-gamma), lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). By morphological examination, both monocytes and MDM were stimulated by these activators. Treatment with IFN-gamma resulted in a slight decrease in the expression of [35S]chondroitin sulfate proteoglycan (CSPG) in both monocytes and MDM, whereas LPS treatment increased the [35S]CSPG expression 1.8 and 2.2 times, respectively. PMA, in contrast, decreased the CSPG expression 0.4 times in monocytes, whereas MDM were stimulated to increase the biosynthesis 1.9 times. An increase in the sulfate density of the chondroitin sulfate chains was evident following differentiation of monocytes into MDM due to the expression of disulfated disaccharide units of the chondroitin sulfate E type (CS-E). However, monocytes exposed to PMA did also express disaccharides of the chondroitin sulfate E type. Furthermore, the expression of CS-E in MDM was increased 2 times following PMA treatment. An inactive phorbol ester, phorbol 12,13-diacetate, did not affect the expression of CS-E in either monocytes or MDM when compared with control cultures, suggesting that protein kinase C-dependent signal pathways may be involved in the regulation of sulfation of CSPG. Exposure to LPS or IFN-gamma did not lead to any changes in the sulfation of the chondroitin sulfate chains.
 ...
PMID:Modulation of the expression of chondroitin sulfate proteoglycan in stimulated human monocytes. 276 47


1 2 3 4 5 6 7 Next >>