Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells, causing bronchiolitis, upper respiratory infections, asthma exacerbations, chronic obstructive pulmonary disease exacerbations, and pneumonia in immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an important ligand for both the innate immune receptor, TLR3, and protein kinase R (PKR). One known effect of RSV infection is the increased responsiveness of airway epithelial cells to subsequent bacterial ligands (i.e., LPS). In this study, we examined a possible role for RSV infection in increasing amounts and responsiveness of another TLR, TLR3. These studies demonstrate that RSV infection of A549 and human tracheobronchial epithelial cells increases the amounts of TLR3 and PKR in a time-dependent manner. This leads to increased NF-kappaB activity and production of the inflammatory cytokine IL-8 following a later exposure to dsRNA. Importantly, TLR3 was not detected on the cell surface at baseline but was detected on the cell surface after RSV infection. The data demonstrate that RSV, via an effect on TLR3 and PKR, sensitizes airway epithelial cells to subsequent dsRNA exposure. These findings are consistent with the hypothesis that RSV infection sensitizes the airway epithelium to subsequent viral and bacterial exposures by up-regulating TLRs and increasing their membrane localization.
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PMID:Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. 1642 3

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.
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PMID:Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells. 1697 6

Meningococcal lipooligosaccharide (LOS) induces a strong proinflammatory response in humans during meningococcal infection. We analyzed the role of LOS in the inflammatory response and virulence during the early infectious process in a mouse model of meningococcal respiratory challenge. An lpxA mutant strain (serogroup B) devoid of LOS (strain Z0204) could not persist in the lungs and did not invade the blood. The persistence in the lungs and invasion of the bloodstream by a rfaD mutant expressing truncated LOS with only lipid A and 3-deoxy-d-manno-2-octulosonic acid molecules (strain Z0401) was intermediate between those of the wild-type and Z0204 strains. Both LOS mutants induced acute pneumonia with the presence of infiltrating polymorphonuclear leukocytes in lungs. Although tumor necrosis factor alpha production was reduced in mice infected with the mutant of devoid LOS, both LOS mutants induced production of other proinflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, and the murine IL-8 homolog KC. Together, these results suggest that meningococcal LOS plays a role during the early infectious and invasive process, and they further confirm that other, nonlipopolysaccharide components of Neisseria meningitidis may significantly contribute to the inflammatory reaction of the host.
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PMID:Differential role of lipooligosaccharide of Neisseria meningitidis in virulence and inflammatory response during respiratory infection in mice. 1698 25

Acinetobacter baumannii is a major nosocomial pathogen and frequent cause of hospital-acquired pneumonia, surgical wound infections and sepsis. As very little is known of the endotoxic potential of A. baumannii lipopolysaccharide (LPS) with respect to human cells or of its ability to stimulate inflammatory signalling via human Toll-like receptors (TLRs), the biological activity of these endotoxins was investigated in human monocytic THP-1 cells and in TLR-deficient HEK-293 cells transfected with human TLR2 and TLR4 constructs. Endotoxins derived from five clinical isolates of A. baumannii and one of Acinetobacter 'genomospecies 9' showed high potency, which was comparable to that of Escherichia coli strain R1 NCTC 13114 LPS, in the induction of the Limulus amoebocyte reaction and interleukin 8 and tumour necrosis factor alpha release from THP-1 cells. Whole UV-killed cells of A. baumannii and Acinetobacter 'genomospecies 9' stimulated both TLR2- and TLR4-dependent signalling, whereas pure endotoxins of all investigated strains induced signalling via TLR4, but not TLR2.
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PMID:Acinetobacter baumannii lipopolysaccharides are potent stimulators of human monocyte activation via Toll-like receptor 4 signalling. 1724 95

Streptococcus agalactiae (S. agalactiae) can cause severe pneumonia, sepsis and meningitis in neonates and remains one of the most prevalent causes of invasive neonatal infections. During the course of infection, S. agalactiae colonizes and invades a number of host compartments, thereby interacting with different host tissues. Deletion of the scpB-lmb region, coding for the C5a peptidase and the laminin-binding protein Lmb, respectively, resulted in a 64% decreased invasion of S. agalactiae into human brain microvascular endothelial cells (HBMEC). Decreased invasion was also seen in lmb mutant strains lmb-k1 and lmb-k2 (74% and 69% reduction, respectively). Finally, host cell invasion was significantly reduced in competition experiments with either purified recombinant laminin-binding protein by 46% or a polyclonal antibody directed against the laminin-binding protein of S. agalactiae by 45%. The S. agalactiae scpB-lmb mutant induced an equal amount of the neutrophil chemoattractant interleukin (IL)-8 release in comparison to the wild-type. Taken together, our studies support the conclusion that Lmb promotes invasion of S. agalactiae into HBMEC but does not play a role in IL-8 release from HBMEC.
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PMID:Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. 1740 16

Pneumonia virus of mice (PVM; family Paramyxoviridae, subfamily Pneumovirinae) is a natural respiratory pathogen of rodent species and an important new model for the study of severe viral bronchiolitis and pneumonia. However, despite high virus titers typically detected in infected mouse lung tissue in vivo, cell lines used routinely for virus propagation in vitro are not highly susceptible to PVM infection. We have evaluated several rodent and primate cell lines for susceptibility to PVM infection, and detected highest virus titers from infection of the mouse monocyte-macrophage RAW 264.7 cell line. Additionally, virus replication in RAW 264.7 cells induces the synthesis and secretion of proinflammatory cytokines relevant to respiratory virus disease, including tumor necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), macrophage inflammatory proteins 1alpha and 1beta (MIP-1alpha and MIP-1beta) and the functional homolog of human IL-8, mouse macrophage inflammatory peptide-2 (MIP-2). Identification and characterization of a rodent cell line that supports the replication of PVM and induces the synthesis of disease-related proinflammatory mediators will facilitate studies of molecular mechanisms of viral pathogenesis that will complement and expand on findings from mouse model systems.
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PMID:Efficient replication of pneumonia virus of mice (PVM) in a mouse macrophage cell line. 1754 63

Burkholderia cenocepacia is an important pulmonary pathogen in individuals with cystic fibrosis (CF). Infection is often associated with severe pulmonary inflammation, and some patients develop a fatal necrotizing pneumonia and sepsis ('cepacia syndrome'). The mechanisms by which this species causes severe pulmonary inflammation are poorly understood. Here, we demonstrate that B. cenocepacia BC7, a potentially virulent representative of the epidemic ET12 lineage, binds to tumour necrosis factor receptor 1 (TNFR1) and activates TNFR1-related signalling pathway similar to TNF-alpha, a natural ligand for TNFR1. This interaction participates in stimulating a robust IL-8 production from CF airway epithelial cells. In contrast, BC45, a less virulent ET12 representative, and ATCC 25416, an environmental B. cepacia strain, do not bind to TNFR1 and stimulate only minimal IL-8 production from CF cells. Further, TNFR1 expression is increased in CF airway epithelial cells compared with non-CF cells. We also show that B. cenocepacia ET12 strain colocaizes with TNFR1 in vitro and in the lungs of CF patients who died due to infection with B. cenocepacia, ET12 strain. Together, these results suggest that interaction of B. cenocepacia, ET12 strain with TNFR1 may contribute to robust inflammatory responses elicited by this organism.
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PMID:Burkholderia cenocepacia ET12 strain activates TNFR1 signalling in cystic fibrosis airway epithelial cells. 1769 31

Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with 'cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammatory cytokine responses to different TLR ligands. Here, we report the increase in pro-inflammatory cytokines TNF-alpha and IL-8, following TLR2 and TLR4 stimulation in a larger cohort of 25 additional patients with HIES, and provide a meta-analysis of the TLR data in HIES.
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PMID:Toll-like receptor stimulation induces higher TNF-alpha secretion in peripheral blood mononuclear cells from patients with hyper IgE syndrome. 1826 86

The purpose of this study was to determine cord blood cytokine levels and their relationship with morbidity and mortality in neonates with prolonged, premature rupture of membranes (PPROM). Forty two premature neonates of 29-35 weeks gestational age with PPROM exceeding 24 hours were considered as the PPROM group and simultaneously, 41 premature neonates without PPROM were considered as the control group. All the neonates were admitted to the Neonatology Unit for further evaluation of subsequent complications such as early neonatal sepsis, pneumonia, intraventicular haemorrhage (IVH), respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC) and chronic lung disease (CLD). Cord blood and mothers' blood samples were obtained during delivery in both groups and tested for IL-6, IL-8 and TNF-alpha levels. Twenty one percent of patients with PPROM had histological chorioamnionitis. The risk for developing early neonatal sepsis increased significantly in neonates whose mothers had histological chorioamnionitis (p < 0.05). There was a statistically significant relationship between PPROM and risk of developing NEC (p < 0.05); no significant increase was seen as regards early neonatal sepsis, IVH, RDS, pneumonia, or BPD. The mean IL-8 levels in cord blood and mothers' serum were significantly higher in the PPROM group (p < 0.001, p< 0.005). In addition, IL-6 levels found in mothers' serum were significantly higher than those found in the control group (p < 0.01). However, levels in cord blood were similar (p > 0.05). TNF-alpha levels were similar in both groups (p > 0.05). Neonates who developed NEC had higher IL-8 levels in their cord blood when compared to those without NEC (p < 0.05). In conclusion, the presence of PPROM increases the risk of chorioamnionitis. In addition, PPROM increases the risk of NEC, and patients who developed NEC had significantly higher cord blood IL-8 values. We may conclude that patients with PPROM and higher IL-8 levels in cord blood might be considered as at possible risk of NEC.
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PMID:Cord blood cytokine levels in neonates born to mothers with prolonged premature rupture of membranes and its relationship with morbidity and mortality. 1829 72

Bacterial alveolar invasion is followed by an inflammatory response. A systemic extension of the compartmentalized immune response has been described in patients with severe pneumonia. The data suggest that some antimicrobials may induce a differential release of cytokines. We conducted a prospective, randomized study in adult patients with severe pneumococcal pneumonia to measure the effects of ceftriaxone and levofloxacin in the systemic cytokine expression over time. Demographic, clinical characteristics, and severity scores were recorded. The serum concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10, and IL-1 receptor agonist were measured at 0, 24, 72, and 120 h. A total of 32 patients were included in the study. Both groups were homogeneous in terms of age, comorbidities, severity of disease, and corticosteroid or statin use. With the single exception of IL-1beta, all cytokines were detected in venous blood. All of the cytokines studied showed a similar pattern of progressive decrease over time. No significant differences in the concentrations of any of the cytokines studied were found, with the exception of TNF-alpha, for which lower concentrations were obtained at 120 h in the levofloxacin group (P = 0.014). Basal oxygen saturation (P = 0.034) and heart rate (P = 0.029) returned to normal values earlier in the levofloxacin arm. We demonstrated that in patients with severe pneumococcal pneumonia pro- and anti-inflammatory responses could be detected in venous blood, representing a systemic extension of the compartmentalized response. Treatment with a beta-lactam agent or a fluoroquinolone has different effects on cytokine production and its systemic expression, impacting the clinical course of the disease.
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PMID:Systemic expression of cytokine production in patients with severe pneumococcal pneumonia: effects of treatment with a beta-lactam versus a fluoroquinolone. 1842 93


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