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)

When cows develop endometritis after birth, Escherichia coli and Arcanobacterium pyogenes are usually the most prominent bacteria present in bovine uterine lochial secretions. A. pyogenes alone is rarely found in the course of a disturbed puerperium. This was confirmed in this study, since average and high-grade uterine contaminations were always associated with the presence of both bacteria. The contamination grade was positively correlated with uterine polymorphonuclear granulocyte (PMN) numbers and negatively correlated with blood PMN numbers. Whether E. coli and A. pyogenes affect the phenotype and function of bovine PMN in a similar or differential way was subject to in vitro studies. PMN were tested in the presence of washed bacterial fragments or culture supernatants taken as a source for soluble and/or secreted bacterial products. Fragments and soluble products differed only quantitatively in their effects on PMN. Usually, long-time exposure (24h) of PMN to fragments induced the strongest effects. Accelerated death of granulocytes was only moderately induced by both E. coli and A. pyogenes products. Both E. coli and A. pyogenes products induced the enhanced expression of a membrane molecule detected by mAb IL-A110 and of CD11b. Expression of other surface structures remained largely unchanged (MHC class I, CD11c). Functional parameters of PMN (phagocytosis; generation of reactive oxygen species, ROS; antibody-independent cellular cytotoxicity, AICC) generally declined after pre-incubation for 24h with products of E. coli or A. pyogenes. Interestingly, soluble products of A. pyogenes stimulated the phagocytosis of PMN. However, co-incubation with E. coli products abrogated this stimulatory effect. The results supply evidence for similar modes of action of the gram-negative E. coli and the gram-positive A. pyogenes on bovine PMN. Alterations in PMN function and phenotype are mainly triggered by direct contact between bacterial fragments and PMN. Inhibition experiments with polymyxin B demonstrated that E. coli-mediated effects were not solely due to the action of lipopolysaccharide. The dominant functional depression of neutrophils by E. coli products strengthens the suggestion that the earlier appearance of E. coli in the uterus may support the co-infection of this organ by A. pyogenes at later times.
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PMID:Influence of Escherichia coli and Arcanobacterium pyogenes isolated from bovine puerperal uteri on phenotypic and functional properties of neutrophils. 1126 94

beta-Defensins are epithelium-derived antimicrobial peptides that function in the host's innate defense. We identified the first member of the rat beta-defensin family, beta-defensin-1 (BD-1), in the kidney and determined its nucleotide sequence. It was predicted to be a 37-amino-acid peptide. Rat BD-1 mRNA was expressed most abundantly in the kidney, next in skin, tongue, esophagus, and uterus, followed (at low levels) by brain, trachea, stomach, urinary bladder, and ovary. BD-1 gene expression in rat kidney was not increased by lipopolysaccharide administration. BD-1 gene expressions in the kidneys of diabetic rodent models, cholecystokinin-insensitive Otsuka Long-Evans Tokushima Fatty rats, leptin-insensitive obese (fa/fa) Wistar rats, and db/db mice, were significantly lower than those of their lean littermates. BD-1 reduction may be in part responsible for the high incidence of urinary tract infections in diabetes mellitus.
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PMID:Nucleotide sequence and expression of rat beta-defensin-1: its significance in diabetic rodent models. 1134 Mar 53

The aim of this study was to investigate the distribution of inducible isoform of nitric oxide synthase (iNOS) in the porcine uterus after infusions of Escherichia coli endotoxin (lipopolysaccharide, LPS). In the group I (treated; n=6), 1 mg of LPS was infused into both the left and right uterine horn starting from the 4th to the 10th day of the estrous cycle, twice a day. In the group II (control; n=6), saline was infused into the uterus. The uterine horns were collected on the 14th day of the estrous cycle. Cryostat sections from the paraformaldehyde fixed tissues were stained immunohistochemically to estimate the distribution of iNOS. The luminal and glandular epithelium was stained more intensely for iNOS in the LPS-treated gilts than in the control animals. After LPS infusions, iNOS staining in vascular endothelial cells was also more intense than that observed in the controls. The present study has revealed that infusions of LPS into the porcine uterus result in an increase in the intensity of iNOS staining in some structures of this organ and supports our earlier data that NO can mediate an inflammatory effect of LPS in the uterus.
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PMID:Immunoreactivity of iNOS in porcine uterus after infusions of Escherichia coli endotoxin. 1137 13

To assess directly the role of protein kinase C (PKC)epsilon in the immune system, we generated mice that carried a homozygous disruption of the PKCepsilon locus. PKCepsilon(-/-) animals appeared normal and were generally healthy, although female mice frequently developed a bacterial infection of the uterus. Macrophages from PKCepsilon(-/-) animals demonstrated a severely attenuated response to lipopolysaccharide (LPS) and interferon (IFN)gamma, characterized by a dramatic reduction in the generation of NO, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta. Further analysis revealed that LPS-stimulated macrophages from PKCepsilon(-/-) mice were deficient in the induction of nitric oxide synthase (NOS)-2, demonstrating a decrease in the activation of IkappaB kinase, a reduction in IkappaB degradation, and a decrease in nuclear factor (NF)kappaB nuclear translocation. After intravenous administration of Gram-negative or Gram-positive bacteria, PKCepsilon(-/-) mice demonstrated a significantly decreased period of survival. This study provides direct evidence that PKCepsilon is critically involved at an early stage of LPS-mediated signaling in activated macrophages. Furthermore, we demonstrate that in the absence of PKCepsilon, host defense against bacterial infection is severely compromised, resulting in an increased incidence of mortality.
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PMID:Protein kinase Cepsilon is required for macrophage activation and defense against bacterial infection. 1169 89

It is believed that failure of the maternal immune system to actively support embryonic development, through production of the appropriate cytokine network, might be responsible for embryonic death. Thus, the aim of this study was to evaluate the possible involvement of cytokines such as tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta2 (TGF-beta2), which are crucial for normal embryonic development, in the early stages of mechanisms that mediate induced pregnancy loss. The early stages of the resorption process induced by lipopolysaccharide (LPS) were characterized by blood accumulation in the vicinity of the embryo, preceding any visible embryonic damage. At that time, immunohistochemical analysis revealed an increased expression of TNF-alpha in the primary and secondary decidua, which was reduced as the resorption process was completed. In contrast, TGF-beta2 expression was decreased in the primary and secondary decidua, as well as in the glandular epithelium, at all the times assessed. Maternal immunopotentiation with granulocyte macrophage-colony stimulating factor (GM-CSF), which controls maternal immune activities supporting normal embryonic development, decreased the resorption rate in LPS-treated mice while normalizing the expression of TNF-alpha and TGF-beta2 in the uterus of these animals throughout the ongoing resorption process. These results indicate a possible role for maternal immunopotentiation with GM-CSF in the mechanisms mediating the early stages of pregnancy loss, possibly via modulation of TNF-alpha and TGF-beta2 activity.
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PMID:Cytokine expression in the uterus of mice with pregnancy loss: effect of maternal immunopotentiation with GM-CSF. 1188 17

The natural antibiotic molecules, beta-defensins 1 and 2 (HBD1/2) and secretory leukocyte protease inhibitor (SLPI), have an important role in mucosal defence and are present in the uterus. This study details their regulation in primary endometrial epithelial cells and in two endometrial cell lines (MFE/HES). Cells were treated with proinflammatory molecules and mimics of infection [lipopolysaccharide (LPS) and lipoteichoic acid (LTA)]. mRNA for HBD1, HBD2 and SLPI was detected in primary endometrial epithelial cells using real-time quantitative PCR. HBD1 mRNA was present at very low levels preventing conclusive study of its regulation. However, HBD2 mRNA expression was increased by interferon-gamma, interleukin (IL)-1beta alone and IL-1beta+tumour necrosis factor (TNF)-alpha. SLPI mRNA was not affected by proinflammatory mediators, although protein levels fell in the presence of IL-1beta+TNFalpha. LPS had little effect on antimicrobial expression. However, there was a trend towards increased expression with LTA treatment for 4-8 h. Antimicrobial expression in endometrial cell lines was similar to that in primary cells, although SLPI was increased by IL-1beta+TNFalpha treatment. These results suggest that in endometrium some natural antibiotics (e.g. SLPI) may be constitutively expressed providing a basal level of protection, while others (e.g. HBD2) are inducible allowing maximal antimicrobial activity during infection. Natural antimicrobials will have an important role in endometrium in protecting against infection.
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PMID:Regulation of natural antibiotic expression by inflammatory mediators and mimics of infection in human endometrial epithelial cells. 1191 82

We demonstrated that rat kinin B(1) receptors displayed a ligand-independent constitutive activity, assessed through inositol phosphate production in transiently or stably transfected human embryonic kidney 293A cells. Substitution of Ala for Asn(130) in the third transmembrane domain resulted in additional constitutive activation of the B(1) receptor. The constitutively active mutant N130A receptor could be further activated by the B(1) receptor agonist des-Arg(9)-bradykinin. To gain insights into the physiological function of the B(1) receptor, we have generated transgenic mice overexpressing wild-type and constitutively active mutant receptors under the control of human cytomegalovirus immediately early gene enhancer/promoter. The rat B(1) receptor transgene expression was detected in the aorta, brain, heart, lung, liver, kidney, uterus, and prostate of transgenic mice by reverse transcription-polymerase chain reaction/Southern blot analysis. Transgenic mice were fertile and normotensive. Overexpression of B(1) receptors exacerbated paw edema induced by carrageenan and rendered transgenic mice more susceptible to lipopolysaccharide-induced endotoxic shock. Interestingly, the hemodynamic response to kinins was altered in transgenic mice, with des-Arg(9)-bradykinin inducing blood pressure increase when intravenously administered. Our study supports an important role for B(1) receptors in modulating inflammatory responses and for the first time demonstrates that B(1) receptors mediate a hypertensive response to des-Arg(9)-bradykinin.
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PMID:Overexpression of kinin B1 receptors induces hypertensive response to des-Arg9-bradykinin and susceptibility to inflammation. 1241 34

Nitric oxide (NO) fulfils important functions during pregnancy and has a role in implantation, decidualization, vasodilatation and myometrial relaxation. However, at high concentrations, such as those that are produced in sepsis, NO has toxic effects as it is a free radical. The aim of this study was to characterize uterine and decidual NO production in lipopolysaccharide (LPS)-induced embryonic resorption in mice and to determine which isoforms of nitric oxide synthase (NOS) take part. LPS produced 100% embryonic resorption at 24 h, with complete fetus expulsions at 48 h. Decidual and uterine NO production were increased by LPS, with maximum production at 6 h. This increase was due to the induction of expression of inducible nitric oxide synthase (iNOS) isoform in the decidua and uterus, and neuronal nitric oxide synthase (nNOS) isoform in the decidua, as detected by western blot analysis and immunohistochemistry. LPS increased iNOS expression in decidual and myometrial cells and increased nNOS expression in decidual cells. In addition, LPS caused fibrinolysis and infiltration of mesometrial decidua by macrophages positive for iNOS and CD14 (LPS receptor). Endothelial nitric oxide synthase (eNOS) was found in decidual and uterine arteries but LPS did not modify its expression. LPS induced CD14 expression in endometrial glands, and this could have amplified the inflammatory response. Aminoguanidine, an inhibitor of iNOS activity, totally reversed the LPS-induced embryonic resorption. This result could be explained by an inhibition of the increase in NO production but also by an inhibition of the cellular infiltration and fibrinolysis. These results show that NO fulfils a fundamental role in LPS-induced embryonic resorption.
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PMID:The fundamental role of increased production of nitric oxide in lipopolysaccharide-induced embryonic resorption in mice. 1262

In the present study, we investigated the effect of nitric oxide (NO) and prostaglandins (PGs) on the production of arachidonate and L-arginine metabolites. We found that in the estrogenized rat uterus lipopolysaccharide (LPS) 5mg/kg induced NO and PGs synthesis simultaneously. The uteri were incubated with different doses of an NO donor: NP 300 and 600 microM. The results indicate that both doses of NP produce a significant increase (P<0.01) in all prostanoids evaluated. The stimulatory effect was completely reversed by the addition of 2 microg/ml of hemoglobin (Hb), an NO scavenger. However, NOS inhibitor, N(G)-L-monomethyl arginine had no effect on basal prostanoid production. We also studied NO synthesis in the presence of different PGs concentration. We found that PGF(2alpha) and PGD(2) were capable of reversing LPS stimulation on NO synthesis (P<0.05), in all the doses evaluated. On the other hand, PGE(2) 10(-10) and 10(-9)M potentated LPS effect (P<0.001). These results suggest that in the estrogenized rat uterus, the synthesis of cyclooxygenase metabolites is positively regulated by NO, while NO synthesis regulation depends on the PGs evaluated.
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PMID:Crosstalk between nitric oxide synthase and cyclooxygenase metabolites in the estrogenized rat uterus. 1262 24

We have identified and characterized a novel single span transmembrane leucine-rich repeat protein, synleurin, that renders cells highly sensitive to the activation by cytokines and lipopolysaccharide (LPS). The major part of the extracellular domain consists of a leucine-rich repeats (LRR) cassette. The LRR central core has 12 analogous LRR repeating modules arranged in a seamless tandem array. The LRRs are most homologous to that of chondroadherin, insulin-like growth factor binding proteins, platelet glycoprotein V, slits, and toll-like receptors. Synleurin expression was detected at low levels in many tissues, including smooth muscle, brain, uterus, pancreas, cartilage, adipose, spleen, and testis. When synleurin is ecotopically expressed in transfected cells, the cells exhibit amplified responses to bFGF, EGF, PDGF-B, IGF-1, IGF-2, and LPS. Synleurin gene (slrn) maps to human chromosome at 5q12. The name synleurin reflects its synergistic effect on cytokine stimulation and its prominent leucine-rich repeats.
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PMID:Synleurin, a novel leucine-rich repeat protein that increases the intensity of pleiotropic cytokine responses. 1276 27


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