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)

Female BALB/c mice were immunized intranasally with the mouse pneumonitis biovar of Chlamydia trachomatis and subsequently challenged in the ovarian bursa (C. trachomatis immunized, C. trachomatis challenged). Two groups of mice served as controls. One group was sham immunized intranasally with mock-infected HeLa 229 cell extracts and was challenged in the ovarian bursa with C. trachomatis MoPn (sham immunized, C. trachomatis challenged). The second control group was sham immunized and not challenged (sham immunized, nonchallenged). Before challenge, the C. trachomatis-immunized, C. trachomatis-challenged animals mounted a significant humoral response as shown by high immunoglobulin G (IgG), IgM, and IgA levels and high levels of neutralizing antibodies in serum and moderate IgG and IgA titers in vaginal secretions. Reactivity by Western blot (immunoblot) to the lipopolysaccharide, 30-, 40- (major outer membrane protein), and 60-kDa cysteine-rich proteins and 75- and 100-kDa chlamydial components could be demonstrated. However, reactivity to the 60-kDa heat shock protein was only observed 22 days after challenge. In addition, this group of animals mounted a significant immune response to chlamydial antigens, as shown by a lymphocyte proliferation assay, compared with the sham-immunized nonchallenged mice. After intrabursal challenge, there was no C. trachomatis shedding from the vagina in the C. trachomatis-immunized, C. trachomatis-challenged animals, while 63% of the sham-immunized, C. trachomatis-challenged mice had a positive C. trachomatis culture. In addition, histological sections from the genital tract showed, at 2 weeks postchallenge, a marked acute inflammatory reaction in the sham-immunized, C. trachomatis-challenged animals while in the C. trachomatis-immunized, C. trachomatis-challenged mice there was minimal inflammatory reaction. When the animals were mated, only 12% of the mice from the sham-immunized, C. trachomatis-challenged mice were fertile. In contrast, 94 and 80% of the sham-immunized, nonchallenged and C. trachomatis-immunized, C. trachomatis-challenged mice, respectively, were fertile.
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PMID:Protection against infertility in a BALB/c mouse salpingitis model by intranasal immunization with the mouse pneumonitis biovar of Chlamydia trachomatis. 803 6

The glmU gene product of Escherichia coli was recently identified as the N-acetylglucosamine-1-phosphate uridyltransferase activity which catalyzes the formation of UDP-N-acetylglucosamine, an essential precursor for cell wall peptidoglycan and lipopolysaccharide biosyntheses (D. Mengin-Lecreulx and J. van Heijenoort, J. Bacteriol. 175:6150-6157, 1993). Evidence that the purified GlmU protein is in fact a bifunctional enzyme which also catalyzes acetylation of glucosamine-1-phosphate, the preceding step in the same pathway, is now provided. Kinetic parameters of both reactions were investigated, indicating in particular that the acetyltransferase activity of the enzyme is fivefold higher than its uridyltransferase activity. In contrast to the uridyltransferase activity, which is quite stable and insensitive to thiol reagents, the acetyltransferase activity was rapidly lost when the enzyme was stored in the absence of reducing thiols or acetyl coenzyme A or was treated with thiol-alkylating agents, suggesting the presence of at least one essential cysteine residue in or near the active site. The acetyltransferase activity is greatly inhibited by its reaction product N-acetylglucosamine-1-phosphate and, interestingly, also by UDP-N-acetylmuramic acid, which is one of the first precursors specific for the peptidoglycan pathway. The detection in crude cell extracts of a phosphoglucosamine mutase activity finally confirms that the route from glucosamine-6-phosphate to UDP-N-acetylglucosamine occurs via glucosamine-1-phosphate in bacteria.
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PMID:Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. 808 70

Tumour necrosis factor (TNF) is synthesized initially as a membrane-bound precursor which is then cleaved to yield soluble, mature protein. The 26,000 MW TNF precursor isolated from the lysate of activated RAW 264.7 (mouse macrophage) cells by immunoprecipitation was used to identify pro-TNF cleavage enzyme in the same cells. A significant amount of mature protein was formed in samples containing Nonidet P-40 (NP-40)-lysed cells, whereas sonicated cells showed negligible activity. Most of the cleavage activity in macrophages was localized in the membrane/particulate fraction and remained largely insoluble after sonication or treatment with 2 mM EDTA/1 M NaCl, indicating that the enzyme is associated with the membrane/particulate fraction. The crude cleavage activity in membrane/particulate was partially inhibited by a spectrum of serine, cysteine and aspartate proteinase inhibitors, whereas secretion of TNF from activated macrophages was inhibited exclusively by serine and serine/cysteine proteinase inhibitors. This result suggested that, among heterogenous pro-TNF cleavage activities, the enzyme responsible for the processing of TNF is a serine proteinase. Pro-TNF cleavage activity was present in non-stimulated macrophages and decreased significantly 8 hr after lipopolysaccharide (LPS) stimulation, suggesting that it is negatively regulated after an initial burst of TNF synthesis.
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PMID:Pro-tumour necrosis factor cleavage enzyme in macrophage membrane/particulate. 824 55

Direct cytotoxicity of black-pigmented anaerobic rods was studied on the confluent monolayer of human gingival fibroblasts in vitro. Only strains of Porphyromonas gingivalis caused morphological alteration (cell-rounding) and notable depression of viability of fibroblasts. To determine the location of the cytotoxicity, bacterial surface components, i.e., outer membrane, lipopolysaccharide, fimbriae and outer membrane vesicles were prepared from P. gingivalis and their cytotoxicity was assessed. Among these preparations, only outer membrane vesicles are supposed to have high affinity to human gingival fibroblasts, and the cytotoxicity of outer membrane vesicles was found to be much stronger than that of the other constituents. This cytotoxic factor seemed to consist largely of protein and to be associated with the enzyme activity of outer membrane vesicles. The effects of some protease inhibitors and L-cysteine on the cytotoxicity of outer membrane vesicles suggest that the mechanism of cell-rounding is different from that of cell death.
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PMID:Cytotoxicity of Porphyromonas gingivalis toward cultured human gingival fibroblasts. 824 6

A series of N-(mercaptoalkyl)thiazolidine-2-thiones and their derivatives were synthesized and evaluated for hepatoprotective activities against Propionibacterium acnes-lipopolysaccharide (P. acnes-LPS)-induced liver injury in mice and in vitro lipid peroxide (LPO) formation in rat liver microsomes. Reaction of N-(p-methoxybenzylthioalkyl)cysteine methyl ester (11) with 1,1'-thiocarbonyldiimidazole followed by deprotection gave the corresponding thiazolidine-2-thione derivatives. Among the compounds synthesized, 1a and 2a showed the most potent hepatoprotective activities against P. acnes-LPS-induced liver injury. Compounds 1a-f and 4 inhibited LPO formation in vitro. Compounds 1a and 2a were chosen for further pharmacological evaluations.
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PMID:Synthesis of thiazolidine-2-thione derivatives and evaluation of their hepatoprotective effects. 833 34

An in vitro cell culture system was used to study the effect of interferon gamma (IFN-gamma) on Chlamydia trachomatis growth and differentiation. The effect of IFN-gamma on chlamydiae was dose-dependent. IFN-gamma at 2 ng/ml completely inhibited chlamydial growth and differentiation; however, persistent infection was established when chlamydiae were cultured with IFN-gamma at 0.2 ng/ml. Persistent infection was characterized by the development of noninfectious atypical chlamydial forms from which infectious progeny could be recovered only when IFN-gamma was removed from the culture system. Analysis of persistently infected cells by immunofluorescent microscopy and immunoblotting with specific antibodies revealed that the atypical chlamydial forms had near-normal levels of the 60-kDa heat shock protein, an immunopathologic antigen, and a paucity of the major outer membrane protein, a protective antigen. Furthermore, steady-state levels of other outer membrane constituents, such as the 60-kDa cysteine-rich outer membrane protein and lipopolysaccharide, were greatly reduced. If IFN-gamma causes similar events to occur in vivo, then persistently infected cells could augment the pathogenesis of the chronic inflammatory sequelae that follow chlamydial infection by serving as depots of antigen capable of stimulating a sustained inflammatory response.
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PMID:Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. 838 6

CAP37 (cationic antimicrobial protein of molecular mass 37 kDa) is a multifunctional protein isolated from the granules of human neutrophils. It is antibiotic and chemotactic and binds lipopolysaccharide. A synthetic peptide, amino acid sequence NQGRHFCGGALIHARFVMTAASCFQ, based on residues 20-44 of CAP37 protein mimics its antibiotic and lipopolysaccharide binding action. Peptide 20-44, at the concentrations tested, has antibacterial activity against Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus. The bactericidal action of the peptide was pH dependent, with maximum activity at pH 5.0 and pH 5.5 and decreased activity at pH 7.0. Various truncations, substitutions, and other modifications in the sequence deteriorate its activity. Free sulfhydryl groups and/or disulfide bridge formation are required for optimum antibiotic activity, since substitution of serines for, or alkylation of, cysteine residues 26 and 42 eliminates bactericidal activity. Evidently amino acids 20-44 represent an important, perhaps principal, antibacterial domain of CAP37. This peptide should provide new insight into the mechanism of antimicrobial activity of CAP37 and may serve as a model for new, useful, synthetic antibiotics.
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PMID:Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes. 850 27

To investigate the effect of the heme moiety of malaria pigment, hemozoin, on phagocyte functions, mouse macrophages were fed with insoluble beta-hematin, the synthetic heme-polymer chemically identical to the native pigment, or the soluble monomer, hematin. Production of inflammatory cytokines, interleukin 1 (IL1), tumor necrosis factor alpha (TNF alpha), and nitric oxide (NO) was assayed in the supernatants after stimulation with lipopolysaccharide. The results indicate that both beta-hematin and hematin induce a dose-dependent inhibition of macrophage production of TNF alpha and NO, but not of IL1. One-hour pretreatment with soluble hematin inhibited production of cytotoxic mediators by more than 50% compared to controls, while 6-hr exposure was necessary for insoluble beta-hematin to induce the same level of inhibition. However, the same treatment did not modify the production of TNF alpha and NO by mouse microglia cell lines. The inhibition was partially counterbalanced by adding sulphydryl group donors such as 2-mercaptoethanol, glutathione, or N-acetyl-cysteine during the preincubation time. The results of the present study confirm the inhibitory role of malaria pigment and show that such effect is due to the heme moiety and may be selective for the production of cytotoxic mediators by specific phagocytes. The implications of these findings in the control of malaria infection and disease and in the pathogenesis of severe malaria are discussed.
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PMID:The heme moiety of malaria pigment (beta-hematin) mediates the inhibition of nitric oxide and tumor necrosis factor-alpha production by lipopolysaccharide-stimulated macrophages. 854 91

The 170-kDa subunit of the galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica mediates adherence to human colonic mucins and intestinal epithelium as a prerequisite to amebic invasion. The Gal-lectin is an immunodominant molecule and a protective antigen in the gerbil model of amebiasis. Tumor necrosis factor alpha (TNF-alpha) produced by activated macrophages enhances nitric oxide-dependent cytotoxicity in host defense against E. histolytica. The purpose of this study was to identify the Gal-lectin epitopes which stimulate TNF-alpha production by macrophages. Murine bone marrow-derived macrophages (BMMs) exposed to Gal-lectin (100-500 ng/ml) stimulated stable expression of TNF-alpha mRNA (8-fold increase) and TNF-alpha production similar to that of lipopolysaccharide-stimulated cells (100 ng/ml). Polyclonal anti-lectin serum specifically inhibited TNF-alpha mRNA induction in response to the Gal-lectin but not to lipopolysaccharide. Anti-lectin monoclonal antibodies 8C12, H85 and 1G7, which recognize nonoverlapping epitopes of the cysteine-rich region of the 170-kDa heavy subunit, inhibited both amebic adherence to mammalian cells and Gal-lectin-stimulated TNF-alpha mRNA expression by BMMs,but monoclonal antibody 7F4 did neither. As these inhibitory antibodies map to amino acids 596-1082 of the 170-kDa Gal-lectin, our results have identified the functional region that mediates amebic adherence and TNF-alpha mRNA induction in BMMMs; thus, this region of the Gal-lectin is a subunit vaccine candidate.
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PMID:Identification of the galactose-adherence lectin epitopes of Entamoeba histolytica that stimulate tumor necrosis factor-alpha production by macrophages. 861 66

It has been known for a long time that heme oxygenase (HO) is a key enzyme in heme catabolism, and it was found to act as an oxidative-stress protein to produce carbon monoxide, which has similar actions to those of nitrogen monoxide. We examined transcriptional control of the HO gene in mouse M1 (myeloleukemia) cells during treatment with lipopolysaccharide (LPS; an oxidative reagent). Since the promoter region of this gene in human cells contains a 12-O-tetradecanoyl- phorbol-13-acetate(TPA)-responsive element (TRE) and a nuclear-factor-kappa B-responsive element. HO mRNA expression might be regulated by an oxidative activation pathway. We investigated activation of the HO gene after treatment of M1 cells with LPS. Upon treatment with LPS, H2O2 was produced, the nuclear proto-oncogenes fos and jun were activated, then the HO gene was activated. The extent of transcriptional activation of the fos, jun and HO genes in M1 cells treated with LPS was strongly reduced by a scavenger of oxygen radicals (N-acetyl-L-cysteine), but a specific inhibitor of protein kinase C only reduced transcriptional activation by 10-20%. These results suggest that LPS may be an oxidative reagent. Some oxidative reagents (e.g., H2O2) are strong activators of NF-kappa B, and therefore we treated M1 cells with H2O2. Essentially the same extends of transcriptional activation of the fos, jun and HO genes were observed as those observed after LPS treatment. Super-shift assays with DNA that contained the TRE motif revealed that the Fos and Jun proteins from nuclei of M1 cells treated with LPS and H2O2 bound weakly to the TRE motif, and, in assays with DNA that contained the NF-kappa B motif, nuclear protein from M1 cells treated with H2O2 or LPS bound strongly to the NF-kappa B motif. These results strongly suggest that the HO gene in M1 cells is mainly activated by LPS through oxidative activation of NF-kappa B due to production of H2O2.
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PMID:Lipopolysaccharide activates transcription of the heme oxygenase gene in mouse M1 cells through oxidative activation of nuclear factor kappa B. 877 98


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