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)

TGF-beta has been implicated in scarring and tissue fibrosis. Most cells secrete TGF-beta as a high molecular weight, latent complex that must be processed to a lower molecular weight, biologically active form. A number of molecules are involved in this activation step including the mannose 6-phosphate/insulin-like growth factor-II receptor, tissue transglutaminase, thrombospondin, plasmin, and others. Here we describe a rapid macrophage-based system for TGF-beta1 activation, which could be used for screening potential anti-fibrotic agents. The system employs transformed mouse peritoneal macrophages treated with lipopolysaccharide as a cell line capable of activating latent TGF-beta. The activation mechanism in our system involves mannose 6-phosphate/insulin-like growth factor-II receptor and transglutaminase. The activation of latent TGF-beta in this system can be prevented by the addition of mannose-6-phosphate but not mannose-1-phosphate. In addition, transglutaminase inhibitors, antibodies to thrombospondin, insulin-like growth factor-II in the presence of its binding protein IGFBP-2, but not IGFBP-1, suppressed the activation of TGF-beta. Anti-inflammatory molecules, such as hydrocortisone, when added to LPS-treated macrophages, inhibited TGF-beta activation by a mechanism, that may involve downregulation of transglutaminase expression. In summary, this new, rapid and reproducible system allows testing molecules for their ability to inhibit TGF-beta activation, thus providing a screening method for potential anti-scarring molecules.
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PMID:Characterization of a macrophage-based system for studying the activation of latent TGF-beta. 1073 58

Hemolymph coagulation in arthropods plays key roles in host defense, including sealing wounds to staunch bleeding and immobilizing invading microorganisms. We have previously reported that horseshoe crab transglutaminase (TGase) promotes cross-linking of a clotting protein (coagulin) with hemocyte-derived proteins (proxins), resulting in the formation of stable coagulin fibrils. Here we show that TGase also cross-links proxins to another hemocyte-derived protein named stablin. Stablin is a cysteine-rich protein of 131 residues. Surface plasmon resonance analysis revealed the specific interaction of stablin with proxin-1 at K(d) = 4.0 x 10(-9) m. Stablin was predominantly localized in the large granules of hemocytes and secreted by lipopolysaccharide-induced exocytosis. Interestingly, stablin bound to chitin at K(d) = 1.5 x 10(-8) m, as determined by using a quartz-crystal microbalance. Stablin also interacted with lipopolysaccharides and lipoteichoic acids and exhibited bacterial agglutinating activity against Gram-positive and -negative bacteria. Immunostaining showed that stablin is co-localized with coagulin in the clotting fibrils that effectively trap bacteria. Moreover, an anti-stablin antibody strongly inhibited the proper formation of the clotting fibrils. These data suggest that stablin promotes the formation of the clotting mesh and the immobilization of invading microbes at injury sites. In arthropods, the TGase-mediated cross-linking may play an important role in the initial stage of host defense, wound closure, and healing, as in the case of mammals.
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PMID:A cysteine-rich protein from an arthropod stabilizes clotting mesh and immobilizes bacteria at injury sites. 1785 45

The tissue expressions of nine immune related genes in apparently healthy Pacific white shrimp Litopenaeus vannamei were analyzed by conventional RT-PCR, quantitative real time PCR (qPCR) and in situ hybridisation. The nine genes were beta-glucan binding protein-high density lipoprotein (BGBP-HDL), lipopolysaccharide-beta-glucan binding protein (LGBP), haemocyanin, prophenoloxidase (proPO), transglutaminase (TGase), crustins, penaeidins (PEN), cytosolic manganese superoxide dismutase (cMnSOD), and lysozyme. Transcripts of all nine genes were detected in all tissues with differential expression levels when examined by RT-PCR and qPCR. BGBP-HDL, LGBP and haemocyanin were mainly expressed in the hepatopancreas and their expressions levels were about 1/10-1/3 those of beta-actin. Their expressions in other tissues were relatively limited. ProPO, TGase, crustins, PEN-3, and lysozyme showed the highest levels of expression in haemocytes and the lowest in hepatopancreas. Their expression levels in the haemocytes were 3 (PEN-3) to 10(-2) (proPO) times those of beta-actin. In contrast to the other genes, cMnSOD showed higher expression levels in haemolymph related organ, stomach and muscle; and lower expression levels in haemocyte, migut, neural ganglion and hepatopancreas. When examined by in situ hybridisation, hepatopancreatic F cells were found to be the major cell type that produced transcripts of BGBP-HDL, LGBP and haemocyanin. On the other hand, circulatory haemocytes and haemocytes infiltrated in various tissues contributed to the expressions of proPO, TGase, crustins, PEN-3 and lysozyme. Both hepatopancreatic F cell and haemocyte generated cMnSOD transcripts. Using in situ hybridisation, the present study is the first to show the tissue distributions of BGBP-HDL, LGBP, haemocyanin, TGase, crustins and cMnSOD in healthy white shrimp. The present results provide a baseline data of physiological expressions for the genes that are important in immune activation and modulation in Pacific white shrimp and a guideline of tissue or organ sampling for effective gene expression analyses for future immunological studies.
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PMID:Tissue expressions of nine genes important to immune defence of the Pacific white shrimp Litopenaeus vannamei. 1796 9

In mammals, the cornified cell envelope forms beneath the plasma membrane in epithelia and provides a vital physical barrier consisting of insoluble proteins cross-linked by transglutaminase (TGase). In the horseshoe crab Tachypleus tridentatus, TGase is stored in hemocytes and secreted in response to the simulation of bacterial lipopolysaccharides. Here we characterized a TGase substrate designated as caraxin that was identified in horseshoe crab cuticle. One of the homologs, caraxin-1, possessed a unique domain structure consisting of N-and C-terminal heptad repeats and a central domain with a tandem-repeated structure of a pentapeptide. Western blotting showed the specific localization of caraxin-1 in sub-cuticular epidermis. Moreover, we identified the pentapeptide motif to be a chitin-binding unit. Analytical ultracentrifugation revealed that caraxin-1 exists as an oligomer with 310-350 kDa, which is approximately 20-mer based on the molecular mass of the monomer. The oligomers were cross-linked by TGase to form an elaborate mesh with honeycomb structures, which was electron-microscopically found to be different from the clotting mesh triggered by lipopolysaccharide-induced hemocyte exocytosis. We determined several cross-linking sites in the N-and C-terminal domains of caraxin-1. The replacements of Leu to Pro at positions 36 and 118 in caraxin-1 reduced the alpha-helix content, which destroyed the TGase-dependent mesh, thus indicating the importance of the N-and C-terminal domains for the proper mesh formation. In arthropods, TGase-dependent protein cross-linking may be involved in the initial stage of host defense at the sub-cuticular epidermis, as in the case of mammalian skin.
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PMID:An arthropod cuticular chitin-binding protein endows injured sites with transglutaminase-dependent mesh. 1796 1

Time-series changes in transcript abundance of nine genes encoding important immune proteins in haemocytes or hepatopancreas of Pacific white shrimp Litopenaeus vannamei fed daily in a 1-week feeding trial diets containing three levels (0%, 0.2% or 1%) of beta-1,3-glucan from Schizophyllum commune were quantified by real-time PCR. As a whole, the immune modulation elicited by beta-glucan is bimodal, one swift reaction of up- or down-regulation occurred within 24h and a delayed regulation was commenced as late as 3-7days. Haemocyanin, crustin, prophenoloxidase (proPO) and transglutaminase (TGase) did not respond to the glucan treatment. While penaeidin 3 (Litvan PEN3) was swiftly down-regulated (0-24h), lysozyme and cytosolic manganese superoxide dismutase (cMnSOD) were swiftly up-regulated (0-24h). In contrast, the two pattern recognition proteins (PRPs), beta-glucan binding protein-high density lipoprotein (BGBP-HDL) and lipopolysaccharide/beta-glucan binding protein (LGBP), showed a delayed up-regulation. Their expressions were not maximized until as late as 72h or 7days, respectively, which coincide with the initiation of reported immune enhancement (6-24days) of PO and SOD activity, phagocytosis and superoxide anion production in penaeid shrimp receiving glucan-containing diet. These immune responses could be the downstream effects of the two PRP gene up-regulation that predispose the shrimp to a state of high immune responsiveness. Increased dosage of beta-glucan from 2 to 10gkg(-1) diet did not affect the expressions of the genes, indicating the sufficiency of beta-glucan supplementation at 2gkg(-1) diet.
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PMID:Differential time-series expression of immune-related genes of Pacific white shrimp Litopenaeus vannamei in response to dietary inclusion of beta-1,3-glucan. 1802 7

Bordetella bronchiseptica is a pathogen of humans and animals that colonizes the respiratory tract. It produces a lipopolysaccharide O antigen that contains a homopolymer of 2,3-dideoxy-2,3-diacetamido-L-galacturonic acid (L-GalNAc3NAcA). Some of these sugars are found in the uronamide form (L-GalNAc3NAcAN), and there is no discernible pattern in the distribution of amides along the chain. A B. bronchiseptica wbmE mutant expresses an O polysaccharide unusually rich in uronamides. The WbmE protein localizes to the periplasm and catalyzes the deamidation of uronamide-rich O chains in lipopolysaccharide purified from the mutant, to attain a wild-type uronamide/uronic acid ratio. WbmE is a member of the papain-like transglutaminase superfamily, and this categorization is consistent with a deamidase role. The periplasmic location of WbmE and its acceptance of complete lipopolysaccharide as substrate indicate that it operates at a late stage in lipopolysaccharide biosynthesis, after polymerization and export of the O chain from the cytoplasm. This is the first report of such a modification of O antigen after assembly. The expression of wbmE is controlled by the Bordetella virulence gene two-component regulatory system, BvgAS, suggesting that this deamidation is a novel mechanism by which these bacteria modify their cell surface charge in response to environmental stimuli.
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PMID:Post-assembly modification of Bordetella bronchiseptica O polysaccharide by a novel periplasmic enzyme encoded by wbmE. 1901 65

The peripheral membrane protein, protein 4.2, is one of the most abundant protein components of the erythrocyte membrane. Protein 4.2 has an important role in red cell membrane structure, its absence due to natural mutations in humans or gene knockout in mice has a detrimental effect on membrane stability and results in hereditary spherocytosis. It is known to be a point of connection between the band 3 complex and the Rhesus protein complex, through its associations with band 3 and CD47 and also via interactions with the cytoskeletal protein ankyrin. Considering its relatively high abundance and importance in stability of the erythrocyte membrane, protein 4.2 has proved a somewhat neglected protein in recent years. In this review we will summarize our current understanding of protein 4.2, discuss its known interactions and describe the effects and implications of protein 4.2 deficiency. Based on protein 4.2's close homology with transglutaminase family proteins, we propose a new speculative "open" homology structure for protein 4.2 that may represent the active, membrane associated protein 4.2 molecule in red blood cells and also explain the dependence of protein 4.2 on band 3 binding for stability.
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PMID:Protein 4.2: a complex linker. 1926

The multifunctional enzyme, transglutaminase 2 (TG2), can be found intracellularly, in the extracellular matrix and on the cell surface. Cell surface TG2 (csTG2) could not be detected by TG2-specific antibodies or autoantibodies on immunocompetent cells. A supposedly csTG2-specific antibody, 6B9, was recently shown to actually react with CD44. Though the importance of TG2-mediated deamidation of gluten in the pathogenesis of celiac disease has been well recognized, it is not known in which intestinal cells or cell compartment the deamidation occurs. Duodenal dendritic cells (DCs) can be directly involved in gluten-reactive T-cell activation. Here we use blood monocyte-derived dendritic cells (iDC) and macrophages (MPhi) as a model for intestinal antigen-presenting cells (APCs) and show that they contain large amounts of TG2. We found that TG100, a commercial TG2-specific monoclonal antibody can recognize TG2 on the surface of these cells, that is monocyte-derived APCs express surface-associated TG2. TG2 expression was found on the surface of individual tunica propria cells in frozen small bowel tissue sections from both normal and celiac subjects. We also demonstrate that the pool of TG2 on the surface of iDCs can be catalytically active, hence it might directly be involved in the deamidation of gliadin peptides. Bacterial lipopolysaccharide (LPS) increased the level of TG2 on the surface of maturing DCs, supporting the hypothesis that an unspecific inflammatory process in the gut may expose more transglutaminase activity.
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PMID:Transglutaminase 2 is expressed and active on the surface of human monocyte-derived dendritic cells and macrophages. 2000 1

Crayfish do not have larval stage as other crustacean such as penaeid shrimp they spawn their eggs until hatching and what hatches out from the eggs are miniature crayfish known as juveniles. In order to address the question whether immune genes are initially expressed during the embryo development in the egg stage, the expression of some immune-related genes: prophenoloxidase (proPO), peroxinectin, hemocyanin, anti-lipopolysaccharide factor (ALF), plcrustin, astakine-1, 2 and transglutaminase (TGase) were determined in the middle phase of crayfish embryo development. Furthermore, immune challenge was used to determine the immune response of eggs by immersing them in a solution of the highly pathogenic bacterium Aeromonas hydrophila. Semi-quantitative RT-PCR analysis showed that all tested genes are present except proPO in this phase of crayfish embryo development and none of the genes tested changed their expression following immersion in A. hydrophila. The proPO transcript has been reported from hemocytes in crustaceans and it plays crucial roles in crustacean immune response. This may indicate that the development of immune-competent hemocytes in this stage of crayfish embryo is not completed and the egg shell as such plays an important role as a shield in protecting the embryo from bacteria and maybe also other pathogens.
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PMID:Expression of immune-related genes in one phase of embryonic development of freshwater crayfish, Pacifastacus leniusculus. 2006 Apr 76

Suppression subtractive hybridization (SSH) was employed to identify yellow head virus (YHV)-responsive genes from the hemocytes of the black tiger shrimp, Penaeus monodon. Two SSH cDNA libraries were constructed to identify viral responsive genes in the early (24I) and late (48/72I) phases of YHV infection. From 240 randomly selected clones from each library, 155 and 30 non-redundant transcripts were obtained for the early and late libraries, respectively. From these clones, 72 and 16, respectively, corresponded to known genes (E-values < 1 x 10(-4)) that could be categorized according to their putative functions. The upregulated genes identified as likely to be associated with cell defense and homeostasis were found at a high proportion in the 24I SSH library, but not in 48/72I SSH library implying that these immune molecules participate in viral defense immunity in the early phase of YHV infection whereas their expressions were suppressed in the late phase of infection. Novel YHV-responsive genes were uncovered from these SSH libraries including caspases, histidine triad nucleotide-binding protein 2, Rab11, beta-integrin, tetraspanin, prostaglandin E synthase, transglutaminase, Kazal-type serine proteinase inhibitor and antimicrobial peptides. Among these YHV-responsive genes, several have been previously reported to participate in defense against white-spot syndrome virus (WSSV) implying that YHV infection in shrimp induces similar host immune responses as observed during WSSV infection. The expression of four apparently upregulated immune-related genes identified from the two SSH libraries, anti-lipopolysaccharide factor isoform 6 (ALFPm6), crustin isoform 1 (crustinPm1), transglutaminase and Kazal-type serine proteinase inhibitor isoform 2 (SPIPm2), was evaluated by real-time RT-PCR to reveal differential expression in response to YHV infection at 6, 24, 48 and 72 h post-infection. The results confirmed their differential expression and upregulation, and thus verified the success of the SSHs and the likely involvement of these genes in shrimp antiviral mechanisms.
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PMID:Identification of genes expressed in response to yellow head virus infection in the black tiger shrimp, Penaeus monodon, by suppression subtractive hybridization. 2006 3


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