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)

The aim of this study was to investigate the relationship between the plasma levels of chemokine CCL-2/MCP-1 and acute graft-versus-host disease (aGVHD) and/or idiopathic pneumonia syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ELISA assays were used to detect the plasma level of CCL-2/MCP-1 of 22 patients who received allo-HSCT, including 14 patients without or with grade I, 8 patients with grade II - IV aGVHD, respectively. 8 out of 22 patients were also diagnosed with IPS clinically. The dynamic changes of the plasma levels of CCL-2/MCP-1 chemokine and its correlation with aGVHD and/or IPS were analysized retrospectively. The results showed that the plasma levels of CCL-2/MCP-1 in the patients with moderate and serious aGVHD (grade II - IV) significantly increased, as compared with that prior to allo-HSCT (p < 0.05). The plasma levels of CCL-2/MCP-1 in the patients with aGVHD and/or IPS were higher significantly than those without any of these complications (p = 0.001). The retrospective analysis indicated that the plasma levels of CCL-2/MCP-1 in the patients with IPS significantly increased (p = 0.006). It is concluded that plasma level of CCL-2/MCP-1 correlates with aGVHD and/or IPS, and plays a role in the pathogenesis of these complications.
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PMID:[Correlation of chemokine CCL-2/MCP-1 level in the plasma with aGVHD and idiophathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation]. 1871 72

Avian influenza A (H5N1) viruses cause severe disease in humans, characterized by rapidly progressive pneumonia, multiorgan dysfunction, and high mortality. Poor clinical outcome is associated with high viral load in throat specimens and frequent detection of virus in feces and blood. The latter finding indicates the potential of the virus to disseminate in humans, similar to what occurs in mammals and birds, which is supported by evidence in autopsy studies of virus in extrapulmonary tissues such as liver and brain. Beside direct virus-induced tissue damage, an intense inflammatory response to the virus likely contributes to disease pathogenesis. In vitro and animal experiments showed that H5N1 viruses induce cytokine production in macrophages and respiratory epithelium. In accordance, human H5N1 infections are characterized by increased plasma chemokine and cytokine concentrations, the levels of which correlate with pharyngeal virus load and clinical outcome. Although antiviral therapy forms the mainstay of treatment, the impact of oseltamivir on H5N1-associated mortality seems limited so far. Explanations for this include late institution of treatment, suboptimal dosing and drug delivery, and development of drug resistance, the latter of which may not be a rare event. The focus of clinical management should be on preventing virus and immune-mediated damage by early diagnosis and effective antiviral treatment with regimens, preferably parenteral, that minimize the risk of resistance development.
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PMID:H5N1 transmission and disease: observations from the frontlines. 1882 May 78

Community-acquired pneumonia (CAP) is associated with high morbidity and mortality, and Streptococcus pneumoniae is the most prevalent causal pathogen identified in CAP. Impaired pulmonary host defense increases susceptibility to pneumococcal pneumonia. S. pneumoniae may up-regulate Toll-like receptor (TLR)-2 expression and activate TLR-2, contributing to pneumococcus-induced immune responses. In the current study, the course of severe murine pneumococcal pneumonia after pulmonary TLR-2-mediated immunostimulation with synthetic macrophage-activating lipopeptide-2 (MALP-2) was examined. Intratracheal MALP-2 application evoked enhanced proinflammatory cytokine and chemokine release, resulting in recruitment of polymorphonuclear neutrophils (PMN), macrophages, and lymphocytes into the alveolar space in WT, but not in TLR-2-deficient mice. In murine lungs as well as in human alveolar epithelial cells (A549), MALP-2 increased TLR-2 expression at both mRNA and protein level. Blood leukocyte numbers and populations remained unchanged. MALP-2 application 24 hours before intranasal pneumococcal infection resulted in increased levels of CCL5 associated with augmented leukocyte recruitment, and decreased levels of anti-inflammatory IL-10 in bronchoalveolar lavage fluid. Clinically, MALP-2-treated as compared with untreated mice showed increased survival, reduced hypothermia, and increased body weight. MALP-2 also reduced bacteremia and improved bacterial clearance in lung parenchyma, as examined by immunohistochemistry. In conclusion, pulmonary immunostimulation with MALP-2 before infection with S. pneumoniae improved local host defense and increased survival in murine pneumococcal pneumonia.
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PMID:Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia. 1893 26

Bacterial pneumonia remains a serious disease. Pattern recognition receptors play an integral role in neutrophil accumulation during pneumonia. Although myeloid differentiation protein (MD)-2 has been recognized as a key molecule for LPS signaling, the role of MD-2 in neutrophil accumulation in the lung during bacterial infection has not been explored. Here, we investigate the role of MD-2 in Escherichia coli LPS-induced lung inflammation and E. coli-induced pneumonia. LPS-induced CD14-independent neutrophil accumulation was abolished in CD14/MD-2(-/-) mice. MD-2(-/-) mice challenged with LPS displayed attenuated neutrophil influx, NF-kappaB activation, cytokine/chemokine expression, and lung histopathology. MD-2(-/-) mice transplanted with MD-2(+/+) bone marrow demonstrated decreased neutrophil influx and cytokine/chemokine expression in the lungs when challenged by LPS. MD-2(-/-) mice infected with E. coli demonstrated reduced neutrophil influx and cytokine/chemokine expression in the lungs, whereas heat-killed E. coli did not induce either neutrophil accumulation or cytokine/chemokine expression in MD-2(-/-) mice infected with E. coli. Furthermore, MD-2(-/-) mice displayed increased bacterial burden in the lungs and enhanced bacterial dissemination. Toll-like receptor (TLR)-5(-/-) mice infected with E. coli exhibited attenuated neutrophil accumulation, whereas MD-2/TLR5(-/-) mice inoculated with E. coli showed further attenuated neutrophil influx and impaired bacterial clearance. Taken together, these new findings demonstrate: (1) the important role of MD-2 in the CD14-independent LPS-mediated cascade of neutrophil influx; (2) the relative importance of bone marrow- and non-bone marrow cell-derived MD-2 in LPS-induced inflammation; and (3) the essential role of MD-2-dependent and MD-2-independent (TLR5) signaling in E. coli-induced neutrophil accumulation and pulmonary host defense.
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PMID:Myeloid differentiation protein-2-dependent and -independent neutrophil accumulation during Escherichia coli pneumonia. 1898 22

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], interleukin 1beta [IL-1beta], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1alpha, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1beta, IL-12 (p40/p70), IFN-gamma, and TNF-alpha; of the chemokines, MIG, MIP-1alpha, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.
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PMID:Tigecycline therapy significantly reduces the concentrations of inflammatory pulmonary cytokines and chemokines in a murine model of Mycoplasma pneumoniae pneumonia. 1913 87

Alveolar type II epithelial cells (ATIIs) are one of the primary targets for influenza A pneumonia. The lack of a culture system for maintaining differentiated ATIIs hinders our understanding of pulmonary innate immunity during viral infection. We studied influenza A virus (IAV)-induced innate immune responses in differentiated primary human ATIIs and alveolar macrophages (AMs). Our results indicate that ATIIs, but not AMs, support productive IAV infection. Viral infection elicited strong inflammatory chemokine and cytokine responses in ATIIs, including secretion of IL-8, IL-6, MCP-1, RANTES, and MIP-1beta, but not TNF-alpha, whereas AMs secreted TNF-alpha as well as other cytokines in response to infection. Wild-type virus A/PR/8/34 induced a greater cytokine response than reassortant PR/8 virus, A/Phil/82, despite similar levels of replication. IAV infection increased mRNA expression of IFN genes IFN-beta, IL-29 (IFN-lambda1), and IL-28A (IFN-lambda2). The major IFN protein secreted by type II cells was IL-29 and ATIIs appear to be a major resource for production of IL-29. Administration of IL-29 and IFN-beta before infection significantly reduced the release of infectious viral particles and CXC and CC chemokines. IL-29 treatment of type II cells induced mRNA expression of antiviral genes MX1, OAS, and ISG56 but not IFN-beta. IL-29 induced a dose-dependent decrease of viral nucleoprotein and an increase of antiviral genes but not IFN-beta. These results suggest that IL-29 exerts IFN-beta-independent protection in type II cells through direct activation of antiviral genes during IAV infection.
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PMID:Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. 1915 75

Lung contusion is a common problem from blunt chest trauma caused by mechanical forces and by exposure to blast overpressure, often with fatal consequences. Lung contusion is also a risk factor for the development of pneumonia, severe clinical acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Infiltrating neutrophils are considered to be central mediators of lung injuries after blunt trauma. Recent studies have demonstrated that antioxidants reduced pulmonary inflammation in different models of lung damage. This study examined the effect of antioxidant N-acetylcysteine amide (NACA) on the progression of lung inflammation after exposure to a moderate level of blast overpressure (140 kPa). Rats were administered with NACA (i.p. 100 mg/kg) or placebo (PBS) 30, 60 min and 24 h after exposure. Nonblasted sham-injected animals served as controls. Neutrophil infiltration measured by myeloperoxidase (MPO) activity in the lung was significantly increased at 2 days after blast and returned to controls at 8 days. This increase corresponded with activation of integrin CD11b mRNA and lung inflammatory chemokine mRNA expression; macrophage inflammatory protein-1 (MIP-1), monocyte chemotactic peptide-1 (MCP-1), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). At 8 days, all inflammatory mediators returned to control levels. In addition, expression of heme oxygenase-1 (HO-1) mRNA increased at 2 days after exposure. No changes were detected in the lung manganase superoxide dismutase (MnSOD) or glutathione reductase (GR) mRNA expression after blast. N-Acetylcysteine amide significantly reduced infiltration of neutrophils and CD11b mRNA activation in lungs, and completely blocked activation of MIP-1, MCP-1 and CINC-1 mRNA. The relatively higher inhibition of chemokine mRNAs compared with reduction in MPO activity and CD11b is in accordance with an antioxidant effect of NACA on reactive oxygen species (ROS) accumulation, rather than by an effect on neutrophil sequestration. The inhibition of HO-1 mRNA activation after blast was likely also related to the drug antioxidant effect.
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PMID:Attenuation of pulmonary inflammation after exposure to blast overpressure by N-acetylcysteine amide. 1917 37

Group B streptococcus (GBS) has been recognized as an ever-growing cause of serious invasive infections in nonpregnant adults, in particular, in association with severe underlying diseases. The most common manifestations include primary bacteremia, urinary tract infections, pneumonia, meningitis, peritonitis, and osteoarticular infections. Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacteria. TLR2 function was investigated in murine GBS-induced sepsis and arthritis in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. Mice were infected with different doses of GBS (10(7), 5 x 10(6), or 10(6) CFU per mouse). Mortality, appearance of arthritis, GBS growth in the organs, and local and systemic cytokine and chemokine production were examined. TLR2(-/-) mice showed earlier and higher mortality rates and increased incidence and severity of arthritis than wt mice at all the infecting doses employed. Histopathological analysis of the joints confirmed clinical observations. TLR2(-/-) mice exhibited a higher microbial load in blood, kidneys, and joints than wt animals. In vitro experiments performed with peritoneal polymorphonuclear cells and macrophages showed a significantly lower bactericidal ability of cells from TLR2(-/-) mice. Increased systemic and local levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-2 accompanied the more severe development of sepsis and arthritis in TLR2(-/-) mice. In conclusion, the lack of TLR2 was associated with an impaired host resistance to GBS infection, likely due to a diminished bacterial clearing and a consequent enhanced inflammatory response.
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PMID:Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease. 1917 17

Cell surface-associated proteolysis plays a crucial role in the migration of mononuclear phagocytes to sites of inflammation. The glycolytic enzyme enolase-1 (ENO-1) binds plasminogen at the cell surface, enhancing local plasmin production. This study addressed the role played by ENO-1 in lipopolysaccharide (LPS)-driven chemokine-directed monocyte migration and matrix invasion in vitro, as well as recruitment of monocytes to the alveolar compartment in vivo. LPS rapidly up-regulated ENO-1 cell-surface expression on human blood monocytes and U937 cells due to protein translocation from cytosolic pools, which increased plasmin generation, enhanced monocyte migration through epithelial monolayers, and promoted matrix degradation. These effects were abrogated by antibodies directed against the plasminogen binding site of ENO-1. Overexpression of ENO-1 in U937 cells increased their migratory and matrix-penetrating capacity, which was suppressed by overexpression of a truncated ENO-1 variant lacking the plasminogen binding site (ENO-1DeltaPLG). In vivo, intratracheal LPS application in mice promoted alveolar recruitment of monocytic cells that overexpressed ENO-1, but not of cells overexpressing ENO-1DeltaPLG. Consistent with these data, pneumonia-patients exhibited increased ENO-1 cell-surface expression on blood monocytes and intense ENO-1 staining of mononuclear cells in the alveolar space. These data suggest an important mechanism of inflammatory cell invasion mediated by increased cell-surface expression of ENO-1.
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PMID:Enolase-1 promotes plasminogen-mediated recruitment of monocytes to the acutely inflamed lung. 1947 49

Necrotizing pneumonia caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates is increasingly common and frequently severe. The early inflammatory response in the lung after CA-MRSA infection remains largely undefined. Additionally, many workers have hypothesized that the Panton-Valentine leukocidin (PVL) is a key virulence determinant in CA-MRSA necrotizing pneumonia. We hypothesized that intratracheal inoculation of rats with a USA300 CA-MRSA isolate would result in early expression of genes involved in the immune response and that this would correlate with inflammation and tissue destruction characteristic of necrotizing pneumonia. In addition, we hypothesized that infection with a PVL deletion mutant would result in an attenuated early host response. Infection of rats with a sublethal inoculum of USA300 (strain LAC) resulted in rapid increased expression of most cytokine, chemokine, and inflammatory receptor gene transcripts studied, as assessed by quantitative real-time reverse transcriptase PCR (qRT-PCR). The increased gene transcription was followed by inflammation, increased bacterial survival in the lungs, and necrotizing pneumonia. Infection with strain LAC and infection with strain LAC Deltapvl (lukSF-PV deletion mutant) resulted in indistinguishable diseases, as assessed by mortality, in vivo bacterial recovery, and pulmonary pathology. Assessment of the transcription of inflammatory genes by qRT-PCR also revealed little difference after infection with LAC and after infection with LAC Deltapvl, either in animals that died or in animals that survived to 24 h after inoculation. We conclude that in a rat model of necrotizing pneumonia, there was an early, brisk inflammatory transcriptional response associated with neutrophil recruitment and tissue destruction. Deletion of lukSF-PV did not alter the early immune response to CA-MRSA in the lung.
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PMID:Transcription of inflammatory genes in the lung after infection with community-associated methicillin-resistant Staphylococcus aureus: a role for panton-valentine leukocidin? 1923 25


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