Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004623 (bacterial infection)
 15,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudomonas aeruginosa is a gram-negative bacterium that causes both acute and chronic lung disease in susceptible patient populations. P. aeruginosa secretes numerous proteins and secondary metabolites, many of which have biological effects that likely contribute to disease pathogenesis. An unidentified small-molecular-weight factor was previously reported to increase IL-8 release both in vitro and in vivo. To identify this factor, we subjected the <3-kDa fraction from P. aeruginosa-conditioned medium to HPLC analysis. A peak fraction that stimulated IL-8 release was found by mass spectrometry to have a molecular mass (MM) of 224 Da. On the basis of this MM and other biochemical properties, we hypothesized that the factor was phenazine-1-carboxylic acid (PCA). Subsequent studies and comparison with purified PCA confirmed this hypothesis. Purified PCA exhibited a number of biological effects in human airway epithelial cells, including increasing IL-8 release and ICAM-1 expression, as well as decreasing RANTES and monocyte chemoattractant protein-1 (MCP-1) release. PCA also increased intracellular oxidant formation as measured by electron paramagnetic resonance and by an intracellular oxidant-sensitive probe. Antioxidants inhibited PCA-dependent increases in IL-8 and ICAM-1, suggesting that oxidants contributed to these effects. However, in contrast to the related phenazine compound pyocyanin, PCA did not oxidize NAD(P)H at physiologically relevant pH, providing preliminary evidence that PCA and pyocyanin may have distinct redox chemistries within the cell. Thus PCA is a biologically active factor secreted by P. aeruginosa that has several activities that could alter the host immune and inflammatory response and thereby contribute to bacterial disease pathogenesis.
 ...
PMID:Phenazine-1-carboxylic acid, a secondary metabolite of Pseudomonas aeruginosa, alters expression of immunomodulatory proteins by human airway epithelial cells. 1276 78

Cystic Fibrosis (CF) lung disease, which is characterized by airway obstruction, chronic bacterial infection, and an excessive inflammatory response, is responsible for most of the morbidity and mortality. Early in life, CF patients become infected with a limited spectrum of bacteria, especially P. aeruginosa. New data now indicate that decreased depth of periciliary fluid and abnormal hydration of mucus, which impede mucociliary clearance, contribute to initial infection. Diminished production of the antibacterial molecule nitric oxide, increased bacterial binding sites (e.g., asialo GM-1) on CF airway epithelial cells, and adaptations made by the bacteria to the airway microenvironment, including the production of virulence factors and the ability to organize into a biofilm, contribute to susceptibility to initial bacterial infection. Once the patient is infected, an overzealous inflammatory response in the CF lung likely contributes to the host's inability to eradicate infection. In response to increased IL-8 and leukotriene B4 production, neutrophils infiltrate the lung where they release mediators, such as elastase, that further inhibit host defenses, cripple opsonophagocytosis, impair mucociliary clearance, and damage airway wall architecture. The combination of these events favors the persistence of bacteria in the airway. Until a cure is discovered, further investigations into therapies that relieve obstruction, control infection, and attenuate inflammation offer the best hope of limiting damage to host tissues and prolonging survival.
 ...
PMID:State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection? 1451 98

Neutrophil-specific granule deficiency (SGD) is a rare, congenital disease characterized by atypical neutrophil structure and function, resulting in recurrent bacterial infections from early infancy. Homozygous recessive mutations in the CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) gene were described in two of five SGD patients, indicating loss of C/EBPepsilon function as the primary genetic defect in this disease. C/EBPepsilon is expressed in murine and human macrophages. Macrophages from the C/EBPepsilon-deficient mice show impaired differentiation, phagocytic activity, and transcription of macrophage-specific genes. To determine if monocyte/macrophage cells are impacted in SGD, we analyzed phenotypic features of peripheral blood (PB) monocytes in a SGD individual lacking functional C/EBPepsilon. Flow cytometric analysis of PB leukocytes revealed aberrant expression of CD45, CD11b, CD14, CD15, and CD16 on cells from the SGD individual. Also, the PB CD14(+) cells from this individual, weakly stained for the monocyte-specific enzyme, nonspecific esterase, and electron microscopic examination, indicated morphologic differences between the SGD cells and those from normal controls. Serum interleukin (IL)-6 levels in the SGD individual during a severe bacterial infection were lower compared with levels in other non-SGD individuals with sepsis. In contrast, serum IL-8 levels were markedly elevated in the SGD individual compared with those of non-SGD individuals in sepsis. PB CD14(+) cells from the SGD individual expressed higher IL-8 mRNA levels compared with normal controls in response to lipopolysaccharide and interferon-gamma. These phenotypic and functional alterations of PB monocytes in the SGD individual suggest that C/EBPepsilon plays a critical role in monocyte/macrophage development of humans and is consistent with observations in the murine system. This study implicates abnormalities in monocytes/macrophages and neutrophils in the onset and development of SGD.
 ...
PMID:Phenotypic and functional alterations of peripheral blood monocytes in neutrophil-specific granule deficiency. 1457 62

Fibroblast-derived interleukin (IL)-8 is thought to have an important role in the orchestration of immuno-participant cells infiltrating the skin and gingiva in response to continuously recurring bacterial infection. Therefore, the IL-8 gene expression should be under tight regulatory control and it might be temporally and spatially limited in inflammatory tissue. The purpose of this study was to examine the aspect of the IL-8 gene expression by fibroblasts stimulated with pro-inflammatory cytokines, IL-1beta and TNF-alpha. In situ hybridisation revealed that fibroblasts did not express IL-8 mRNA whereas keratinocytes and endothelial cells did in IL-1beta- or TNF-alpha-injected mice skin. However, cultured mouse dermal fibroblasts expressed not only IL-8 but also IL-1beta mRNA without stimulation by exogenous IL-1beta and TNF-alpha, and the expression was not enhanced by the exogenous cytokines. A similar result was obtained in late-passage human gingival fibroblasts. These results suggest that fibroblasts remain insensitive to IL-1beta and TNF-alpha so as to induce the IL-8 gene expression in non-inflammatory mice skin. Mouse dermal and late-passage human gingival fibroblasts in vitro are likely to be altered in phenotype into IL-8-producing cells along with the production of IL-1beta. In skin inflammation and periodontal diseases, fibroblasts may express the IL-8 gene even without an exogenous cytokine, IL-1beta or TNF-alpha, during their proliferation similar to the situation in our culture system.
 ...
PMID:Aspects of interleukin-8 gene expression by gingival and dermal fibroblasts stimulated with interleukin-1beta or tumour necrosis factor alpha. 1496 91

Differentiation of hematopoietic stem cells (HSCs) can be influenced by different stimuli, including cytotoxic agents, certain cytokines, and contact with pathogens. Infection may result in dysregulation of these important progenitor cells and therefore interfere with the availability of blood cells. In this study we analyzed the effect of bacterial infection on HSCs concerning surface marker expression and cytokine release. Listeria monocytogenes and Yersinia enterocolitica accelerated maturation of hematopoietic progenitor cells along the myeloid lineage, as demonstrated by the upregulation of CD13, CD14, and costimulatory signals. By screening cytokine secretion, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha were found to be induced by bacterial infection. These data indicate that infection of HSCs with L. monocytogenes and Y. enterocolitica affects the differentiation of CD34(+) hematopoietic progenitors in vitro and may lead to secretion of cytokines that can influence the HSC differentiation capacity and immune response.
 ...
PMID:Bacterial infection of human hematopoietic stem cells induces monocytic differentiation. 1498 33

Necrotizing enterocolitis is a devastating inflammatory condition of the intestine that occurs almost exclusively in premature newborns. Although its exact pathogenesis is unclear, we have postulated that it may result from a predisposition of the immature intestine to mount an unusually robust and damaging response to microbial infection. In support of this idea, we report that the IL-8 response of an immature human enterocyte cell line to bacterial infection was significantly higher than that of a mature enterocyte cell line. The response in both cell lines was flagellin-dependent. Corresponding to the difference in IL-8 production, the immature enterocytes expressed appreciably lower levels of specific IkappaB genes when compared with the mature enterocytes. Similar developmentally regulated differences in cytokine response and IkappaB expression were also seen in primary rat enterocytes, indicating that these observations were not peculiarities of the cell lines. Furthermore, when the level of IkappaBalpha expression was increased in the immature cell line by transfection, the flagellin-dependent IL-8 response was attenuated. Thus, we have demonstrated a previously undescribed developmental regulation of IkappaB expression in the intestine involved in modulating the IL-8 response to bacterial infection, which may contribute to the pathogenesis of age-specific inflammatory bowel diseases such as necrotizing enterocolitis.
 ...
PMID:Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. 1512 21

Toll-like receptors (TLRs) mediate host responses to bacterial gene products. As the airway epithelium is potentially exposed to many diverse inhaled bacteria, TLRs involved in defense of the airways must be broadly responsive, available at the exposed apical surface of the cells, and highly regulated to prevent activation following trivial encounters with bacteria. We demonstrate that TLR2 is enriched in caveolin-1-associated lipid raft microdomains presented on the apical surface of airway epithelial cells after bacterial infection. These receptor complexes include myeloid differentiation protein (MyD88), interleukin-1 receptor-activated kinase-1, and TNF receptor-associated factor 6. The signaling capabilities of TLR2 are amplified through its association with the asialoganglioside gangliotetraosylceramide (Gal beta 1,2GalNAc beta 1,4Gal beta 1,4Glc beta 1,1Cer), which has receptor function itself for many pulmonary pathogens. Ligation of either TLR2 or asialoGM1 by ligands with specificity for either receptor, by Pseudomonas aeruginosa, or by Staphylococcus aureus stimulates IL-8 production through activation of NF-kappa B, as mediated by TLR2 and MyD88. Thus, TLR2 in association with asialo-glycolipids presented within the context of lipid rafts provides a broadly responsive signaling complex at the apical surfaces of airway cells to initiate the host response to potential bacterial infection.
 ...
PMID:TLR2 is mobilized into an apical lipid raft receptor complex to signal infection in airway epithelial cells. 1514 46

The chemokine CCL28 is constitutively expressed by epithelial cells at several mucosal sites and is thought to function as a homeostatic chemoattractant of subpopulations of T cells and IgA B cells and to mediate antimicrobial activity. We report herein on the regulation of CCL28 in human colon epithelium by the proinflammatory cytokine IL-1, bacterial flagellin, and n-butyrate, a product of microbial metabolism. In vivo, CCL28 was markedly increased in the epithelium of pathologically inflamed compared with normal human colon. Human colon and small intestinal xenografts were used to model human intestinal epithelium in vivo. Xenografts constitutively expressed little, if any, CCL28 mRNA or protein. After stimulation with the proinflammatory cytokine IL-1, CCL28 mRNA and protein were significantly increased in the epithelium of colon but not small intestinal xenografts, although both upregulated the expression of another prototypic chemokine, CXCL8, in response to the identical stimulus. In studies of CCL28 regulation using human colon epithelial cell lines, proinflammatory stimuli, including IL-1, bacterial flagellin, and bacterial infection, significantly upregulated CCL28 mRNA expression and protein production. In addition, CCL28 mRNA expression and protein secretion by those cells were significantly increased by the short-chain fatty acid n-butyrate, and IL-1- or flagellin-stimulated upregulation of CCL28 by colon epithelial cells was synergistically increased by pretreatment of cells with n-butyrate. Consistent with its upregulated expression by proinflammatory stimuli, CCL28 mRNA expression was attenuated by pharmacological inhibitors of NF-kappaB activation. These findings indicate that CCL28 functions as an "inflammatory" chemokine in human colon epithelium and suggest the notion that CCL28 may act to counterregulate colonic inflammation.
 ...
PMID:Regulated production of the chemokine CCL28 in human colon epithelium. 1524 61

Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI.
 ...
PMID:Evaluation of IL-8-concentrations in plasma and lysed EDTA-blood in healthy neonates and those with suspected early onset bacterial infection. 1531 62

Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A3, which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase C-dependent manner. These data suggest that bacterial-induced hepoxilin A3 secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections.
 ...
PMID:Polymorphonuclear cell transmigration induced by Pseudomonas aeruginosa requires the eicosanoid hepoxilin A3. 1549 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>