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)

Shigellosis is a major form of bacillary dysentery caused by Shigella infection. Shigella ribosome-based vaccines (SRV), considered among the potent vaccine candidates, are composed of O-antigen and ribosome isolated from S. flexneri 2a. To investigate the immunogenicity and protective efficacy of SRV, mice were vaccinated with SRV via the intranasal (i.n.) route. Interestingly, robust levels of Shigella-derived LPS-specific IgG and IgA Abs and antibody-forming cells were elicited in systemic and mucosal compartments following two i.n. administrations of SRV. Groups of mice receiving i.n. SRV developed milder pulmonary pneumonia upon challenge with virulent S. flexneri 2a than did those receiving parenteral SRV. We further found that the MyD88-dependent TLR2 signal partially mediates SRV-induced mucosal immunity, with the exception of TLR4- and TLR5-governed innate immunity. Most importantly, polymeric immunoglobulin receptor knockout (pIgR-/-) mice, which lack secretory IgA Ab, were afforded less protective efficacy than were wild-type mice. It can be concluded then that SRV is immunogenic and provides protective efficacy in mice. It can also be surmised that a mucosal SRV vaccine would be particularly relevant in targeting shigellosis, which provokes inflammation in the human colon.
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PMID:Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a. 1750 20

The severe and protracted inflammation that characterizes acute lung injury (ALI) is driven by the ongoing recruitment of neutrophils to the lung. Although much of the cytokine signaling responsible for the initial phase of ALI has been elaborated, relatively little is known about the mechanisms governing the recruitment of neutrophils from the bone marrow to the lung in the later period of this disease. Given its previously described chemoattractant effects on marrow neutrophils, we investigated whether stromal-derived factor-1 (SDF-1) (CXCL12) might participate in this later phase of recruitment. Using immunohistochemistry to examine both banked human lung specimens from patients with ALI and lungs from mice with LPS-induced pneumonitis, we found that pulmonary SDF-1 expression increases during ALI. We further determined that both lung SDF-1 protein expression and mRNA expression rise in a delayed but sustained pattern in this mouse model and that the major source of the increase in expression appears to be the lung epithelium. Lastly, we found that expression of the SDF-1 receptor CXCR4 rises in a similar temporal pattern on neutrophils in both the blood and airspace of LPS-injured mice and that Ab-mediated SDF-1 blockade significantly attenuates late but not early pulmonary neutrophilia in this model. These results implicate SDF-1 in neutrophil recruitment to the lung in the later period of acute lung injury and suggest a novel role for this cytokine in coordinating the transition from the inflammatory response to the initiation of tissue repair.
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PMID:Pulmonary stromal-derived factor-1 expression and effect on neutrophil recruitment during acute lung injury. 1754 53

Intubation and mechanical ventilation after burn contribute to pneumonia-related infection. Although postburn presence or absence of endotoxin has been described, inactivation of Toll-like receptor 4 signaling has been shown to improve postburn organ function, suggesting that LPS participates in burn-related susceptibility to infection. We hypothesized that bactericidal/permeability-increasing protein (rBPI) given postburn would attenuate myocardial inflammation/dysfunction associated with postburn septic challenge given 7 days postburn. Rats were given burn over 40% total body surface area, lactated Ringer 4 ml.kg(-1).% burn(-1); burns received either vehicle or rBPI, 1 mg.kg(-1).h(-1) for 48 h postburn. Postburn day 7, subgroups of burns and shams were given intratracheal Klebsiella pneumoniae, 4 x 10(6) CFU to produce burn complicated by sepsis; additional sham and burn subgroups received intratracheal vehicle to produce sham sepsis. Vehicle-treated groups: 1) sham burn + sham sepsis 2) sham burn + sepsis, 3) burn + sham sepsis, 4) burn + sepsis. rBPI-treated groups: 5) sham burn + sham sepsis, 6) sham burn + sepsis, 7) burn + sham sepsis, 8) burn + sepsis. Cardiomyocyte cytokine secretion and myocardial function were studied 24 h after septic challenge, postburn day 8. Pneumonia-related infection 8 days after vehicle-treated burn produced myocyte cytokine secretion (pg/ml), indicated by increased myocyte TNF-alpha, 549 +/- 46; IL-1beta, 50 +/- 8; IL-6, 286 +/- 3 levels compared with levels in sham myocytes (TNF-alpha, 88 +/- 11; IL-1beta, 7 +/- 1; IL-6, 74 +/- 10; P < 0.05). Contractile dysfunction was evident from lower left ventricular pressure +/-dP/dt values in this group compared with sham. rBPI attenuated myocyte cytokine responses to septic challenge and improved contractile function, suggesting that burn-related mobilization of microbial-like products contribute to postburn susceptibility to infection.
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PMID:Bactericidal/permeability increasing protein attenuates the myocardial inflammation/dysfunction that occurs with burn complicated by subsequent infection. 1758 43

Although mainly expressed in neuronal cells, lipocalin-type PGD synthase (L-PGDS) is detected in the macrophages infiltrated to atherosclerotic plaques. However, the regulation and significance of L-PGDS expression in macrophages are unknown. Here, we found that treatment of macrophages with bacterial endotoxin (LPS) or Pseudomonas induced L-PGDS expression. Epigenetic suppression of L-PGDS expression in macrophages blunted a majority of PGD(2) produced after LPS treatment. Chromatin immunoprecipitation assays show that L-PGDS induction was regulated positively by AP-1, but negatively by p53. L-PGDS expression was detected in whole lung and alveolar macrophages treated with LPS or Pseudomonas. L-PGDS overexpressing transgenic mice improved clearance of Pseudomonas from the lung compared with nontransgenic mice. Similarly, intratracheal instillation of PGD(2) enhanced removal of Pseudomonas from the lung in mice. In contrast, L-PGDS knockout mice were impaired in their ability to remove Pseudomonas from the lung. Together, our results identify induction of L-PGDS expression by inflammatory stimuli or bacterial infection, the regulatory mechanism of L-PGDS induction, and the protective role of L-PGDS expression in host immune response. Our study suggests a potential therapeutic usage of L-PGDS or PGD(2) against Pseudomonas pneumonia.
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PMID:Induction and function of lipocalin prostaglandin D synthase in host immunity. 1767 19

Somatostatin released from activated capsaicin-sensitive afferents of the lung inhibits inflammation and related bronchial hyperreactivity presumably via somatostatin 4 receptors (sst(4)). The aim of this study was to examine the effects of TT-232, a heptapeptide sst(4)/sst(1) receptor agonist and J-2156, a high affinity sst(4) receptor-selective peptidomimetic agonist in airway inflammation models. Acute pneumonitis was evoked by intranasal lipopolysaccharide 24 h before measurement. Chronic inflammation was induced by ovalbumin inhalation on days 28, 29 and 30 after i.p. sensitization on days 1 and 14. Semiquantitative histopathological scoring was based on perivascular/peribronchial oedema, neutrophil/macrophage infiltration, goblet cell hyperplasia in the acute model and eosinophil infiltration, mucosal oedema, mucus production and epithelial cell damage in chronic inflammation. Myeloperoxidase activity of the lung was measured spectrophotometrically to quantify granulocyte accumulation and the broncoalveolar lavage fluid was analysed by flow cytometry. Carbachol-induced bronchoconstriction was assessed by unrestrained whole body plethysmography and its calculated indicator, enhanced pause (Penh) was determined. TT-232 and J-2156 induced similar inhibition on granulocyte recruitment and histopathological changes in both models, although macrophage infiltration in LPS-induced inflammation was unaltered by either compounds. Both agonists diminished inflammatory airway hyperresponsiveness. Since their single administration after the development of the inflammatory reactions also inhibited carbachol-induced bronchoconstriction, somatostatin sst(4) receptor activation on bronchial smooth muscle cells is likely to be involved in their anti-hyperreactivity effect. These results suggest that stable, somatostatin sst(4) receptor-selective agonists could be potential candidates for the development of a completely novel group of anti-inflammatory drugs for the treatment of airway inflammation and hyperresponsiveness.
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PMID:Inhibitory effects of synthetic somatostatin receptor subtype 4 agonists on acute and chronic airway inflammation and hyperreactivity in the mouse. 1796 45

Serratia marcescens is an important nosocomial pathogen, which has been especially problematic as a cause of hospital-acquired pneumonia in the past two decades. Treatment of S. marcescens-related infections has been limited by emergence of multiple drug-resistant strains. Thus, the development of alternative agents for the prevention and treatment of Serratia infection is urgently needed. Resveratrol (RSV) is a compound with diverse biological effects including anti-cancer, anti-inflammation, anti-diabetes, and cancer chemoprevention. Whether RSV has in vivo prophylactic or therapeutic potential against infection remains uncharacterized. In the present study, we used a murine acute pneumonia model initiated by intratracheal application of S. marcescens to evaluate whether RSV possesses anti-infection properties. We showed that pretreatment with RSV for 3 days markedly increased alveolar macrophage infiltration, elevated NK cell activity, and decreased bacterial burden in the infected lung with a subsequent decrease in mortality. These effects were associated with significantly less-severe inflammatory phenotypes in lung tissue and bronchoalveolar lavage fluid, including reduced neutrophil infiltration of the lungs, reduced phagocytosis activity, and reduced secretion of cytokines such as TNF-alpha, IL-1beta, and IL-6. To further characterize the underlying mechanism responsible for these effects of RSV, LPS derived from S. marcescens was used to induce acute pneumonia in rats, with or without RSV pretreatment. RSV was shown to ameliorate acute pneumonia via inhibition of the NF-kappaB signaling pathway, including inhibition of IkappaBalpha phosphorylation and subsequent NF-kappaB activation. These findings suggest that RSV might be beneficial as a prophylactic treatment in patients at risk of an episode of S. marcescens-induced acute pneumonia.
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PMID:Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats. 1817 63

SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co-infected with SARS-CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33~90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co-infection with SARS-CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia.
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PMID:Co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice. 1838 Aug 9

CD47 modulates neutrophil transmigration toward the sites of infection or injury. Mice lacking CD47 are susceptible to Escherichia coli (E. coli) peritonitis. However, less is known concerning the role of CD47 in the development of acute lung inflammation and injury. In this study, we show that mice lacking CD47 are protected from LPS-induced acute lung injury and E. coli pneumonia with a significant reduction in pulmonary edema, lung vascular permeability, and bacteremia. Reconstitution of CD47(+/-) mice with CD47(-/-) neutrophils significantly reduced lung edema and neutrophil infiltration, thus demonstrating that CD47(+) neutrophils are required for the development of lung injury from E. coli pneumonia. Importantly, CD47-deficient mice with E. coli pneumonia had an improved survival rate. Taken together, deficiency of CD47 protects mice from LPS-induced acute lung injury and E. coli pneumonia. Targeting CD47 may be a novel pathway for treatment of acute lung injury.
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PMID:CD47 deficiency protects mice from lipopolysaccharide-induced acute lung injury and Escherichia coli pneumonia. 1845 16

LPS binding protein (LBP) is an acute-phase glycoprotein that facilitates LPS activation of immune cells through interactions with CD14 and Toll-like receptor 4. Initially, LBP production was thought to occur exclusively in the liver in response to stimulation with TNF-alpha, IL-1, and IL-6. More recently, it has been shown that type II pneumocytes are also capable of LBP production. Little is known, however, regarding the regulation and or distribution of this protein in response to localized intrapulmonary infection. We performed time-course experiments challenging C3H mice intratracheally with LPS (10 mug). In separate experiments, mice deficient in IL-6 were given the same dose of intratracheal LPS and euthanized 8 h later. Despite the intratracheal route of LPS administration, an increase in plasma LBP concentrations occurred earlier and was of greater magnitude than the increase observed in bronchoalveolar lavage fluid. Liver LBP mRNA increased to a greater extent than did lung LBP mRNA. Whereas the TNF-alpha response remained localized within the alveolar space, IL-6 was increased both locally and in plasma. Of several tissues analyzed, the lung was the greatest producer of IL-6 mRNA. Plasma LBP was significantly decreased in the IL-6-deficient mice compared with wild-type controls challenged with intratracheal LPS. We conclude that lung-derived IL-6 is an important mediator of hepatic LBP up-regulation. We speculate that the disruption of these lung-liver signaling pathways may be important to host response efforts to confine infection to the lung. If impaired, this may be one mechanism underlying the increased mortality observed in patients with liver disease who develop pneumonia.
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PMID:The systemic and pulmonary LPS binding protein response to intratracheal lipopolysaccharide. 1852 Jul 4

Recently, we have shown that female BALB/c mice are highly sensitive to chronic psychological stress. They develop systemic neuroendocrine disturbances, a hypermetabolic syndrome, behavioral alterations and severe immunosuppression with a reduced antibacterial response during experimental infection. Here, we show that chronically stressed mice spontaneously suffered from increased bacterial load in the liver and lung that sustained for up to 10 days after the termination of stress exposure. Immediately after the last chronic stress cycle, splenocytes had a reduced ability to produce IFNgamma after ex vivo stimulation with LPS while showing enhanced inducibility of IL-10. When healthy animals were treated with anti-IFNgamma antiserum the antibacterial response against the small numbers of endogenous bacteria that physiologically penetrate the intestinal barrier was reduced causing increased bacterial burden in the liver. Thus, a deficient antibacterial response to translocated commensals in chronically stressed animals can contribute to long-lasting pneumonia.
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PMID:Pneumonia as a long-term consequence of chronic psychological stress in BALB/c mice. 1857 93


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