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)

The cellular immune response to respiratory syncytial virus (RSV) is felt to contribute to viral clearance and/or the inflammation accompanying pulmonary infections with this virus. Both tumor necrosis factor (TNF) and prostaglandin E2 (PGE2) are important regulatory mediators of the cellular immune response. We examined the production of these mediators from purified human alveolar and blood mononuclear phagocytes (MP) after RSV infection in vitro and compared production induced by virus with that induced by lipopolysaccharide (LPS). RSV infection of alveolar MP did not alter PGE2 production but increased expression of TNF alpha mRNA paralleled by increased secretion of immunoreactive and biologically active TNF. TNF production by alveolar MP was dependent on the infectious dose of virus and occurred early in the viral replication cycle. In contrast, RSV had minimal effects on blood MP production of TNF and PGE2. However, blood MP (and not alveolar MP) infected with RSV and costimulated with LPS demonstrated a 1.7-fold increase in PGE2 levels compared with LPS alone (P less than 0.001). Therefore, RSV has differential effects on human alveolar and blood MP production of these immunoregulatory molecules.
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PMID:Virus-induced alterations in macrophage production of tumor necrosis factor and prostaglandin E2. 226 Jun 74

We studied the permissiveness of human leukocytes, blood monocytes, alveolar macrophages, and cord blood monocytes to infection with respiratory syncytial virus (RSV). Specific immunofluorescence was used to determine the percentage of infected leukocytes. The results indicated that monocytes were the most susceptible human leukocyte to in vitro infection with RSV. Polymorphonuclear leukocytes demonstrated no specific fluorescent staining after 24 h of exposure to RSV, whereas peripheral blood nonadherent mononuclear cells demonstrated a low percentage of positive cells, with a mean of 6 +/- 1% SE. In contrast, 37 +/- 5% of monocytes expressed RSV antigen after viral exposure. Exposure of monocytes to lipopolysaccharide (LPS) for 1 h prior to RSV increased the percentage of infected cells to 48 +/- 6% and stimulated their secretion of prostaglandin E2 (PGE2) and alpha tumor necrosis factor (TNF). Intrinsic mononuclear phagocytic factors influencing the permissiveness to RSV were studied by determining infection of adult and cord blood and alveolar mononuclear phagocytes (MP). Alveolar and blood MP simultaneously isolated from adult donors were similarly infected by RSV, which varied with the viral dose. Cord blood MP were more susceptible to RSV infection than were adult MP, 58 +/- 9% infected versus 37 +/- 5%, respectively (p less than 0.05). Treatment with LPS for 1 h prior to RSV exposure did not increase infection of cord blood MP as seen with adult blood MP. However, LPS can induce human monocytes to secrete cytokines with antiviral activity, and our results indicate that both gamma interferon and TNF, independently or in combination, prevented infection of monocytes in a dose-dependent manner.
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PMID:Respiratory syncytial virus infection of human cord and adult blood monocytes and alveolar macrophages. 247 59

The correlation of clinical and immunological parameters with the duration of respiratory failure was investigated to identify factors determining the clinical outcome of respiratory syncytial virus (RSV) bronchiolitis necessitating mechanical ventilation. At initiation of mechanical ventilation in 30 patients with RSV, production of interleukin (IL)-12 and IL-10 was measured in 48-h peripheral blood cell cultures that were stimulated with lipopolysaccharide and interferon-gamma. The ventilation index (VI)-an indicator of respiratory dysfunction that includes partial pressure of arterial CO2, peak airway pressure, and respiratory rate-correlated with the duration of mechanical ventilation (r=.47; P=.013). Age was not associated with the duration of mechanical ventilation. A highly significant inverse correlation was found between the duration of mechanical ventilation and the production of IL-12 at admission (r=-.62; P<.001). This correlation was independent of VI. No correlation was found between IL-10 production and the duration of mechanical ventilation. It is hypothesized that low monocyte IL-12 response during initial RSV infection adversely affects clinical outcome of patients with severe RSV bronchiolitis.
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PMID:Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis. 1082 82

Airway epithelial cells are unresponsive to endotoxin (lipopolysaccharide (LPS)) exposure under normal conditions. This study demonstrates that respiratory syncytial virus (RSV) infection results in increased sensitivity to this environmental exposure. Infection with RSV results in increased expression of Toll-like receptor (TLR) 4 mRNA, protein, and increased TLR4 membrane localization. This permits significantly enhanced LPS binding to the epithelial monolayer that is blocked by disruption of the Golgi. The increased TLR4 results in an LPS-induced inflammatory response as demonstrated by increased mitogen-activated protein (MAP) kinase activity, IL-8 production, and tumor necrosis factor alpha production. RSV infection also allowed for tumor necrosis factor alpha production subsequent to TLR4 cross-linking with an immobilized antibody. These data suggest that RSV infection sensitizes airway epithelium to a subsequent environmental exposure (LPS) by altered expression and membrane localization of TLR4. The increased interaction between airway epithelial cells and LPS has the potential to profoundly alter airway inflammation.
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PMID:Respiratory syncytial virus up-regulates TLR4 and sensitizes airway epithelial cells to endotoxin. 1456 59

RSV causes annual epidemics of bronchiolitis in winter months resulting in the hospitalization of many infants and the elderly. Dendritic cells (DCs) play a pivotal role in coordinating immune responses to infection and some viruses skew, or subvert, the immune functions of DCs. RSV infection of DCs could alter their function and this could explain why protection after natural RSV infection is incomplete and of short duration. In this study, this interaction between DCs and RSV was investigated using a human primary culture model. DCs were generated from purified healthy adult volunteer peripheral blood monocytes. Effects of RSV upon DC phenotype with RSV primed DCs was measured using flow cytometry. Changes to viability and proliferation of cocultured DCs and T-cells were determined using microscopy with fluorescent dyes (Hoechst 33342 and propidium iodide). DC maturation was not prevented by the RSV challenge. RSV infected a fraction of DCs (10-30%) but the virus replicated slowly in these cells with only small reduction to cell viability. DCs challenged with RSV stimulated T-cell proliferation less well than lipopolysaccharide. This is the first study to demonstrate RSV infection of human monocyte derived DCs and suggests that the virus does not significantly interfere with the function of these cells and potentially may promote cellular rather than humoral responses.
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PMID:Differentiation and immune function of human dendritic cells following infection by respiratory syncytial virus. 1648 51

Respiratory syncytial virus (RSV) infects airway epithelial cells, causing bronchiolitis and pneumonia. Inflammation is mediated by various cytokines secreted from RSV-infected airway epithelial cells, and it promotes the pathogenesis of RSV-related diseases. Fosfomycin (FOF) is approved as a treatment for various bacterial infectious diseases, including respiratory infectious diseases, in Japan. FOF is suggested to exhibit immunomodulatory effects on lipopolysaccharide-stimulated monocytes and T lymphocytes, in addition to its antimicrobial activity. We investigated the effect of FOF on the cytokine production of an airway epithelial cell line, A549, infected with RSV. RSV-induced cytokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin-8 (IL-8), and IL-6, in infected A549 cells. We found that FOF decreased the levels of RSV-induced RANTES and IL-8 but not the level of RSV-induced IL-6. The RANTES promoter was activated by RSV infection. Site-directed mutagenesis analysis of the RANTES promoter showed that NF-kappaB-binding motifs had a critical role in RSV-induced RANTES promoter activity. A luciferase reporter gene assay and a DNA-binding assay indicated that FOF suppressed the NF-kappaB activity induced by RSV infection. These results demonstrate that FOF treatment suppresses the RSV-induced transcription of the chemokines RANTES and IL-8 in airway epithelial cells.
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PMID:Fosfomycin suppresses chemokine induction in airway epithelial cells infected with respiratory syncytial virus. 1936 76

Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)-infected offspring on day 5 post-infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post-infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF-alpha and IL-6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV-infected offspring exposed to DBDE perinatally, but IL-1beta increased. However, in ex vivo lipopolysaccharide stimulation test, the productivity of TNF-alpha in the bronchoalveolar lavage cells, which are mainly primary immune cells responding to RSV infection, prepared from offspring mice exposed to DBDE perinatally was not lower than that in the control. The primary immune cells retained normally the ability of cytokine production after the DBDE exposure. Gene expressions of innate pattern recognition receptors (Toll-like receptor 3 and 4, melanoma differentiation-associated gene-5, and retinoic acid-inducible gene I) in lung tissues were not affected by DBDE exposure. Because the levels of TNF-alpha, IL-6, and IL-1beta are known to be elevated in the lungs of RSV-infected mice, these irregular productions due to perinatal DBDE exposure indicate a disorder of the primary immune response to RSV infection. Thus, perinatal exposure to DBDE was suggested to cause a functional disorder of primary immunity responding to RSV infection.
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PMID:Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally. 2041 25

Cysteinyl leukotriene receptor antagonist (LTRA) is a widely used medicine for asthma. Cysteinyl leukotrienes (cysLTs) are involved in the regulation of dendritic cell (DC) function. However, the effects of LTRA on DC-related antimicrobial immunity against harmful respiratory pathogens remain unknown. The purpose of this study was to examine the effects of LTRA administered in vivo on DC function against representative respiratory pathogens in vitro. Pulmonary DCs were isolated from four groups of mice: control, mite allergen sensitized (AS), and AS mice treated with the corticosteroid dexamethasone (Dex) or with the LTRA pranlukast (Prl). These DCs were incubated with mite allergen, lipopolysaccharide (LPS), Aspergillus fumigatus, or respiratory syncytial virus (RSV). IL-10 and IL-12 production was then determined. Dex treatment significantly inhibited lipopolysaccharide (LPS)-induced IL-10 and IL-12 production as well as baseline IL-12 production in AS mice. The Prl did not significantly inhibit LPS-induced IL-10 and IL-12 production in AS mice. More importantly, Prl significantly increased IL-10 and IL-12 in AS mice after RSV infection. This study shows that LTRA that is used for asthma potentially up-regulates antimicrobial immunity through modulation of DC function against some respiratory infections without immunosuppression.
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PMID:Regulation of dendritic cell functions against harmful respiratory pathogens by a cysteinyl leukotrienes receptor antagonist. 2285 27

Respiratory syncytial virus (RSV) infection is the primary cause of respiratory disease in infants. The formalin-inactivated RSV (FI-RSV) vaccine resulted in an enhanced respiratory disease (ERD) in infants upon natural RSV infection, which is a major obstacle for development of safe and efficacious vaccines. Excessive and uncontrolled Th immune responses could be involved in the ERD. Agonists of TLRs are used as adjuvants to guide the type of immune response induced by vaccines. We evaluated the impact of lipopolysaccharide (LPS), the agonist of TLR4, on ERD as the adjuvant of FI-RSV. The results showed that LPS remarkably inhibited FI-RSV-enhanced lung inflammation, mucus production, airway inflammatory cell infiltration, and inflammatory cytokines following RSV challenge. Interestingly, LPS inhibited both Th2 and Th17 type cytokines in lungs of FI-RSV-immunized mice following RSV challenge, without an increase in the Th1 type cytokines, suggesting a controlled immune response. In contrast, Pam3Cys and Poly(I:C), the agonist of TLR1/2 or TLR3, partly inhibited FI-RSV-enhanced lung inflammation. Pam3Cys inhibited Th17 type cytokine IL-17, but promoted both Th1 and Th2 type cytokines. Poly(I:C) inhibited Th2 and Th17 type cytokines, but promoted Th1 type cytokines. In addition, LPS promoted IgG and IgG2a antibody production, which might provide protection from RSV challenge. These results suggest that LPS inhibits ERD without impairment in antibody production and protection, and the mechanism appears to be related with regulation of Th responses induced by FI-RSV.
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PMID:Lipopolysaccharide Inhibits FI-RSV Vaccine-enhanced Inflammation Through Regulating Th Responses. 3120 4