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)

Prostaglandins (PG) are potent mediators of intercellular communication, and PGE2 at high concentration is immunosuppressive for T-cell-mediated immunity. We studied the kinetics of PGE2 production and the expression of the enzymes related to its synthesis during the course of experimental pulmonary tuberculosis. Secondly, we analysed the pathological and immunological changes produced by the pharmacological suppression of PG production. In BALB/c mice infected via the trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of partial resistance, dominated by type 1 cytokines plus tumour necrosis factor-alpha (TNF-alpha) and expression of the inducible form of nitric oxide synthase (iNOS), followed by a phase of progressive disease. During the early phase of the infection some activated macrophages located in the alveolar-capillary interstitium and in granulomas showed strong PGE2 immunostaining. However, PGE2 concentrations were relatively low and stable. Animals in this early phase of infection were treated with niflumic acid, a potent and specific blocker of cyclo-oxygenase 2, the rate-limiting enzyme of PG production. In comparison with control animals, the suppression of PG synthesis produced higher inflammation and expression of TNF-alpha, interleukin-1alpha and interferon-gamma (IFN-gamma), but almost complete disappearance of iNOS expression, which coexisted with a significant increment of bacterial load. The late progressive phase in this experimental model is characterized by progressive pneumonia, small granulomas and diminished expression of IFN-gamma, TNF-alpha and iNOS in coexistence with high expression of IL-4. Strong PGE2 immunostaining was seen in foamy macrophages localized in the pneumonic areas, and the PGE2 concentration was four-fold higher in this late phase of infection than during the early phase. When PG production was suppressed in animals suffering advanced phase infection, a significant reduction of pneumonia and bacillus load with striking increment of granuloma size was seen, and the expression of IFN-gamma, TNF-alpha and iNOS was also improved. These findings demonstrate a significant participation of PGE2 in the pathogenesis of pulmonary tuberculosis, showing that during the early phase of the infection there are low PGE2 concentrations which contribute to iNOS expression permitting the temporal control of bacillus growth, while the high PGE2 concentrations during the late phase of the disease contribute to down-regulate cell-mediated immunity, permitting disease progression.
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PMID:The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis. 1204 55

Nocardia asteroides causes an acute, necrotizing pneumonia characterized by extensive infiltration of polymorphonuclear neutrophils (PMNs) into the lungs. Although PMNs have historically been classified as end-point cells, recent investigations have indicated that PMNs have the ability to secrete cytokines such as interleukin (IL)-4 and IL-12. This study investigated the ability of PMNs to produce cytokines in a murine model of N. asteroides pulmonary infection. Flow cytometric analysis demonstrated the production of interferon-gamma (IFN-gamma), but not IL-4, by PMNs in response to this infection. IFN-gamma production correlated with peak infiltration of PMNs into the lungs. Cell sorting and enzyme-linked immunosorbent assay were used to confirm cytokine production by cells with nuclear morphology characteristic of PMNs. This is the first report of IFN-gamma production by neutrophils in response to an infection in vivo. These results suggest that PMNs play an important role in directing the host toward a T helper cell type 1 phenotypic response in the lungs.
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PMID:Murine polymorphonuclear neutrophils produce interferon-gamma in response to pulmonary infection with Nocardia asteroides. 1214 29

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia, a chronic nonfatal disease affecting pigs of all ages. The goal of this study was to design DNA vaccines by constructing plasmid pcDNA3/P42, carrying the heat shock protein gene P42 of M. hyopneumoniae, and to evaluate the immune responses elicited in BALB/c mice. The expression of P42 was first examined in transfected NIH 3T3 cells by reverse transcription-PCR to ensure that the construct was functional. The humoral and cell-mediated immune responses induced by the plasmid were further evaluated in BALB/c mice through intramuscular injection. Both immunoglobulin G1 (IgG1) and IgG2a levels were 64 times those of the control groups during the first 8 weeks. The levels of interleukin-2 (IL-2), IL-4, and gamma interferon mRNAs in the immunized animals were elevated, and the proliferation of spleen cells was also enhanced in the immunized animals. The results indicate that pcDNA3/P42 DNA immunization induces both Th1 and Th2 immune responses. In addition, antiserum from the immunized animals was found to inhibit the growth of M. hyopneumoniae. The present study reveals that DNA vaccination could be a new strategy against infection by M. hyopneumoniae and may have potential for developing vaccines for other infectious diseases as well.
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PMID:Expression and immunogenicity of Mycoplasma hyopneumoniae heat shock protein antigen P42 by DNA vaccination. 1259 27

Suppressor of cytokine signaling-1 (SOCS-1) is an essential regulator of cytokine signaling. SOCS-1-/- mice die before weaning with a complex disease characterized by fatty degeneration and necrosis of the liver. This disease is mediated by interferon (IFN) gamma as neonatal mortality fails to occur in SOCS-1-/-IFNgamma-/- mice. However, the immune system of healthy SOCS-1-/-IFNgamma-/- mice is dysregulated with a reduced ratio of CD4:CD8 T cells and increases in some aspects of T cell activation. SOCS-1-/-IFNgamma-/- mice also die before their wild type and IFNgamma-/- counterparts with a range of inflammatory conditions including pneumonia, gut infiltration, and skin ulceration, suggesting that SOCS-1 controls not only IFNgamma signaling, but also other immunoregulatory factors. This study shows that T cells from SOCS-1-deficient mice display hypersensitivity to cytokines that act through the gammac receptor. SOCS-1 expression is induced by interleukin (IL) 2, IL-4, IL-7, and IL-15, and SOCS-1-deficient T cells show increased proliferation and prolonged survival in response to IL-2 and IL-4. Furthermore, IL-2 induced increased STAT5 phosphorylation and CD44 expression in SOCS-1-deficient T cells compared with controls. Hypersensitivity to gammac-dependent cytokines may contribute to abnormal T cell function, as well as the pathology observed in mice lacking SOCS-1.
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PMID:Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other gamma c-dependent cytokines in peripheral T cells. 1266 16

We have studied the changes in the serum level of the following cytokines during the course of treatment of nosocomial pneumonia (NP): pro-inflammatory--IL-1alpha and IL-6, chemoattractive--IL-8, anti-inflammatory--IL-4 and IL-10, and differentiating-activating--IFN-gamma and TNF-alpha. It has been found that at the time of admission of the patients the clinical severity of their condition was correlated with increased levels of all circulating cytokines except for IFN-gamma, the level of which was low. An adequate ethiotropic therapy helped to clear the clinical symptoms of infection and intoxication in 1-2 weeks. The level of circulating pro- and anti-inflammatory cytokines, IL-8, and TNF-alpha was decreasing, however, the level of IFN-gamma did not change significantly during 15 days. The ratio IFN-gamma/IL-10 did not change much but was slightly low during the treatment of the severe form of NP. Radical positive changes in the cytokine dynamics were achieved after the addition of leukinferon to the ethiotropic therapy.
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PMID:Dynamics of cytokines and role of immunocorrection in nosocomial pneumonia. 1268 58

An IgE-dependent histamine-releasing factor (HRF p23; also known as translationally controlled tumor protein or p23) stimulates the release of histamine, IL-4, and IL-13 from a subpopulation of highly allergic donor basophils. It has also been shown to act as a chemoattractant for eosinophils. To elucidate novel functions of HRF p23 in airway inflammation, we examined the effects of human recombinant HRF p23 (hrHRF) on bronchial epithelium and found that hrHRF stimulated the secretions of IL-8 and granulocyte/macrophage colony-stimulating factor by both primary cultures of human bronchial epithelial cells and BEAS-2B cells. In response to hrHRF, these cells induced IL-8 mRNA expression within 4 h. H2O2, but not IL-1 beta or tumor necrosis factor-alpha, stimulated secretion of HRF p23 by BEAS-2B cells, suggesting that oxidative stress may trigger the release of HRF p23 from bronchial epithelial cells. Bronchoalveolar lavage (BAL) from healthy volunteers contained only trivial or undetectable amounts of HRF p23. Significantly higher amounts of HRF p23 were recovered from BAL fluid taken from asthmatic patients, and the amounts of HRF p23 were further elevated in patients with idiopathic eosinophilic pneumonia. Our results demonstrate for the first time that HRF p23 can stimulate nonimmune epithelium. HRF p23 derived from bronchial epithelial cells may regulate complex cytokine networks in eosinophil-dependent inflammation of the human airway.
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PMID:Stimulation of human bronchial epithelial cells by IgE-dependent histamine-releasing factor. 1294 34

Streptococcus pneumoniae infection may result in asymptomatic carriage, mucosal or invasive disease. We hypothesize that self-limiting or fatal disease outcome follows infection with S. pneumoniae differential activation of the host immune response. BALB/c and C57BL/6 mice were inoculated intranasally with S. pneumoniae serotype 3 strain WU2 and serotype 14 strain DW14 and mortality, bacterial load, pathological changes in the lungs and cytokines mRNA levels in the spleen were analysed. No differences between the C57BL/6 and the BALB/c inbred mice were observed except for the severity of their lung pathology and IL-4 expression. Infection of the two mouse strains with S. pneumoniae WU2 resulted in sepsis and death that occurred within 4 days post-inoculation. This death was preceded, in both mouse strains, in an increase over time of the lung bacterial load and bacteraemia. The lung pathology was characterized by diffuse pneumonia with marked congestion of the lungs. Analysis of mRNA expression of cytokines in the spleen revealed no alterations in tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-12 and interferon (IFN)-gamma and induction of IL-10 and IL-4. The two strains of mice survived infection with S. pneumoniae DW14. This was accompanied by a reduction over time of lung bacterial load and bacteraemia. The lung pathology was characterized by focal lymphocyte infiltration and preserved architecture of the organ. Analysis of mRNA expression of cytokines in the spleen revealed a significant decrease in the levels of TNF-alpha, TGF-beta, IL-12 and IFN-gamma mRNA expression, which usually precedes cytokine protein expression. Interestingly, a significant increase in the levels of IL-4 mRNA expression was found in BALB/c mice only. This study suggests that differential activation or evasion of cytokine expression by S. pneumoniae virulent strains determines disease outcome regardless of the host's immunogenetic background.
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PMID:Differential activation of the immune system by virulent Streptococcus pneumoniae strains determines recovery or death of the host. 1297 50

Pneumonitis followed by lung fibrosis is a frequent complication of radiation therapy of chest tumors. A hallmark of these fibrotic lesions is the excessive production and accumulation of extracellular matrix proteins such as type I collagen. In addition to TGF-beta1, IL-4 has been recognized as a potent inducer of collagen gene synthesis in fibroblasts. In this study, we analyzed the regulation of the alpha1(I) procollagen (COL1A1) promoter and the alpha2(I) procollagen (COL1A2) promoter by IL-4 in normal human lung fibroblasts. We provide evidence that the IL-4-induced transcriptional activator STAT6 binds to various sequences within the COL1A1 and COL1A2 promoter. The regulatory function of these regions was tested by reporter gene analysis using 5' deletions of the COL1A1 and COL1A2 promoter fused to the luciferase gene. Interleukin-4 treatment of human fibroblasts transiently transfected with COL1A1 promoter deletion constructs resulted in luciferase activity exceeding that of untreated fibroblasts by 25%, while luciferase activity driven by the COL1A2 promoter was enhanced by about 70% upon IL-4 treatment. A combined action of SP1, NFkappaB, and STAT6 essentially contributes to the IL-4 mediated COL1A2 gene activation. An AP2 site adjacent to the reverse orientated STAT6 consensus motif TTC N(3/4) GCT is located within 205 bases from the transcription start site and seems to support the moderate IL-4-induced COL1A1 gene activation. Interferon-gamma downregulation of transcription is mainly seen with the COL1A1 promoter.
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PMID:Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin-4: analysis of the functional collagen promoter sequences. 1460 27

Mycoplasma hyopneumoniae (Mh) is the primary agent of porcine enzootic pneumonia (PEN), a chronic respiratory disease endemic to pig farms, and characterized histologically by infiltration of mononuclear cells in airways and prominent hyperplasia of the bronchus-associated lymphoid tissue (BALT). To gain further insight into the pathogenesis of PEN, cytokine expression in the lung, with particular attention to the BALT, was examined immunohistochemically in pigs naturally infected with Mh. An increase (P < 0.05) in proinflammatory and immunoregulatory cytokines (especially interleukin [IL]-2, IL-4 and tumour necrosis factor [TNF]-alpha, and to a lesser extent IL-1 [alpha and beta] and IL-6) was detected in the BALT, which showed intense lymphoid hyperplasia. IL-1beta and TNF-alpha were also detected in the bronchoalveolar exudate of infected pigs, and IL-6 and IL-8 were demonstrated in mononuclear cells of the alveolar septa. The results showed that in Mh infection, macrophage and lymphocyte activation results in the expression of a number of cytokines capable of inducing lung lesions and lymphoreticular hyperplasia of the BALT.
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PMID:Immunohistochemical labelling of cytokines in lung lesions of pigs naturally infected with Mycoplasma hyopneumoniae. 1505 34

T-helper-1-like cytokine response and cell-mediated immunity have been shown to be critical in host resistance to Chlamydia trachomatis infection. Using a murine pneumonia model, we compared the susceptibility of C3H/HeN (C3H) and C57BL/6 mice to C. trachomatis mouse pneumonitis (MoPn) infection. C3H mice exhibited significantly higher mortality, greater organism growth and much more severe pathological changes in the lung compared with C57BL/6 mice. However, the pattern of adaptive immune responses including organism-specific delayed-type hypersensitivity, antibody responses and cytokine [interferon-gamma (IFN-gamma), interleukin-12 (IL-12), IL-4, IL-10 and tumour necrosis factor alpha] production by spleen and local draining lymph node cells in these two strains of mice appeared comparable during the process of infection. Interestingly, MoPn growth in the cultured ex vivo macrophages from C3H mice was found to be significantly less inhibited by the exogenous IFN-gamma present in the culture compared to C57BL/6 mice. The lower inhibition of MoPn growth in C3H mice was associated with significantly lower nitric oxide production by the infected macrophages following IFN-gamma stimulation. The data suggest that the cellular events downstream of cytokine production in chlamydia host cells may be important in determining the different susceptibility of hosts to chlamydial infection.
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PMID:Less inhibition of interferon-gamma to organism growth in host cells may contribute to the high susceptibility of C3H mice to Chlamydia trachomatis lung infection. 1505 83


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