Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.7 (BAL)
1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Association between staphylococcal infection and pathogenesis of upper airways disease has been reported. This study aimed to investigate the mechanisms underlying the rat pulmonary inflammation induced by airway exposure to staphylococcal enterotoxin A (SEA). SEA (0.3-10 ng trachea(-1)) caused dose-dependent neutrophil accumulation in BAL fluid, reaching maximal responses at 4 h (25-fold increase for 3 ng trachea(-1)). Significant accumulation of both lymphocytes and macrophages in BAL fluid was also observed at 4 h (2.1- and 1.9-fold increase, respectively, for 3 ng trachea(-1)). At later times (16 h), neutrophil counts in bone marrow (immature forms) and peripheral blood increased by 63 and 81%, respectively. SEA failed to directly induce chemotaxis and adhesion of isolated neutrophils. Analysis of mRNA expression for iNOS, COX-2 and CINC-2 in lung tissue showed an upregulation of these enzymes, which paralleled elevated levels of LTB4, PGE2, TNF-alpha, IL-6 and NO2- in BAL fluid. Expression of CINC-1 was unchanged, whereas CINC-3 was reduced in SEA-treated rats. Incubation of isolated alveolar macrophages with SEA (3 microg ml(-1)) resulted in significant elevations of TNF-alpha and NO2- levels in the cell supernatants. Dexamethasone (0.5 mg kg(-1)), celecoxib (3 mg kg(-1)) and compound 1400 W (5 mg kg(-1)) markedly reduced SEA-induced lung neutrophil influx and NO2- levels in BAL fluid. The lipoxygenase inhibitor AA-861 (100 microg kg(-1)) partly inhibited the neutrophil influx in SEA-treated rats without modifying the NO2- levels. None of these treatments reduced the number of mononuclear cells in BAL fluid (except of dexamethasone, which abolished the increased lymphocyte counts). Our study shows that airways exposure to SEA results in marked neutrophil influx through mechanisms involving increased expressions of CINC-2, iNOS and COX-2, as well as enhanced production of NO, PGE2, LTB4, TNF-alpha and IL-6.
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PMID:Inflammatory mechanisms underlying the rat pulmonary neutrophil influx induced by airway exposure to staphylococcal enterotoxin type A. 1617 Mar 30

Staphylococcus aureus is a gram-positive bacterium that produces several enterotoxins, which are responsible for most part of pathological conditions associated to staphylococcal infections, including lung inflammation. This study aimed to investigate the underlying inflammatory mechanisms involved in leukocyte recruitment in rats exposed to staphylococcal enterotoxin B (SEB). Rats were anesthetized with pentobarbital sodium and intratracheally injected with either SEB or sterile phosphate-buffered saline (PBS, 0.4 ml). Airways exposition to SEB (7.5-250 ng/trachea) caused a dose- and time-dependent neutrophil accumulation in BAL fluid, the maximal effects of which were observed at 4 h post-SEB exposure (250 ng/trachea). Eosinophils were virtually absent in BAL fluid, whereas mononuclear cell counts increased only at 24 h post-SEB. Significant elevations of granulocytes in bone marrow (mature and immature forms) and peripheral blood have also been detected. In BAL fluid, marked elevations in the levels of lipid mediators (LTB(4) and PGE(2)) and cytokines (TNF-alpha, IL-6 and IL-10) were observed after SEB instillation. The SEB-induced neutrophil accumulation in BAL fluid was reduced by pretreatment with dexamethasone (0.5 mg/kg), the COX-2 inhibitor celecoxib (3 mg/kg), the selective iNOS inhibitor compound 1400 W (5 mg/kg) and the lipoxygenase inhibitor AA-861 (200 microg/kg). In separate experiments carried out with rat isolated peripheral neutrophils, SEB failed to induce neutrophil adhesion to serum-coated plates and chemotaxis. In conclusion, rat airways exposition to SEB causes a neutrophil-dependent lung inflammation at 4 h as result of the release of proinflammatory (NO, PGE(2), LTB(4), TNF-alpha, IL-6) and anti-inflammatory mediators (IL-10).
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PMID:Acute pulmonary inflammation induced by exposure of the airways to staphylococcal enterotoxin type B in rats. 1692 Jan 68

Previous studies have reported little correlation between the relative toxicity of particle types when comparing lung toxicity rankings following in vivo instillation versus in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particle types in rats. In the in vivo component of the study, rats were exposed by intratracheal instillation to 1 or 5 mg/kg of the following particle types: (1) carbonyl iron (CI), (2) crystalline silica (CS) (Min-U-Sil 5, alpha-quartz), (3) precipitated amorphous silica (AS), (4) nano-sized zinc oxide (NZO), or (5) fine-sized zinc oxide (FZO). Depending on particle type and solution state, these particles range in size from 90 to 500 nm in size. Following exposures, the lungs of exposed rats were lavaged and inflammation (neutrophil recruitment) and cytotoxicity end points (bronchoalveolar lavage [BAL] fluid lactate dehydrogenase [LDH] values) were measured at 24 h, 1 week, 1 and 3 months postexposure. For the in vitro component of the study, three different culture conditions were utilized. Cultures of (1) rat L2 lung epithelial cells, (2) primary alveolar macrophages (AMs) (collected via BAL from unexposed rats), as well as (3) AM-L2 lung epithelial cell cocultures were incubated with the particle types listed above, and the culture fluids were evaluated for cytotoxicity end points (LDH, 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan [MTT]) as well as inflammatory cytokines (macrophage inflammatory 2 protein [MIP-2], tumor necrosis factor alpha [TNF-alpha], and interleukin-6 [IL-6]) at one (i.e., cytokines) or several (cytotoxicity) time periods. Results of in vivo pulmonary toxicity studies demonstrated that instilled CI particles produced little toxicity. CS particles produced sustained inflammation and cytotoxicity. AS particles produced reversible and transient inflammatory responses. NZO or FZO particles produced potent but reversible inflammation which was resolved by 1 month postinstillation exposure. Results of in vitro pulmonary cytotoxicity studies demonstrated a variety of responses to the different particle types, primarily at high doses. With respect to the LDH results, L2 cells were the most sensitive and exposures to nano- or fine-sized ZnO for 4 or 24 h were more cytotoxic than exposures to CS or AS particles. Macrophages essentially were resistant and epithelial macrophage cocultures generally reflected the epithelial results at 4 and 24 h incubation, but not at 48 h incubation. MTT results were also interesting but, except for nano- and fine-sized ZnO, did not correlate well with LDH results. Results of in vitro pulmonary inflammation studies demonstrated that L2 cells did not produce MIP-2 cytokines, but CS- or AS-exposed AMs and, to a lesser degree, cocultures secreted these chemotactic factors into the culture media. Measurements of TNF-alpha in the culture media by particle-exposed cells demonstrated little activity. In addition, IL-6 secretion was measured in CS, AS, and nano-sized ZnO-exposed cocultures. When considering the range of toxicity end points to five different particle types, the comparisons of in vivo and in vitro measurements demonstrated little correlation, particularly when considering many of the variables assessed in this study-such as cell types to be utilized, culture conditions and time course of exposure, as well as measured end points. It seems clear that in vitro cellular systems will need to be further developed, standardized, and validated (relative to in vivo effects) in order to provide useful screening data on the relative toxicity of inhaled particle types.
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PMID:Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. 1730 Oct 66

In order to evaluate the pulmonary effects and inflammatory mechanisms of ultrafine amorphous silica particles (UFASs), the UFASs suspension was prepared in PBS and intratracheally administered to A/J mice at doses of 0, 2, 10 and 50mg/kg (n=5 per group). Animals were sacrificed at 24h, and 1, 4 or 14 weeks following exposures. At each time point, a bronchoalveolar lavage fluid analysis, histopathological examination, quantitative real-time PCR and immunohistochemistry of the lung tissues were assessed. The intratracheal instillation of UFASs significantly increased the lung weights and total BAL cells following exposures. The histopathological examination revealed that UFASs-induced severe inflammation, with neutrophils, at an early stage and chronic granulomatous inflammation at the later stage. The mRNA and protein levels of IL-1beta, IL-6, IL-8, TNF-alpha, MCP-1 and MIP-2 in lung tissues were significantly increased during the early stages, but there were no changes after weeks 1 (TNF-alpha) or 4 (IL-1beta, IL-6, IL-8, MCP-1 and MIP-2). Instillation of UFASs-induced transient, but very severe lung inflammation. Therefore, the cytokines (IL-1beta, IL-6, IL-8 and TNF-alpha) and chemokines (MCP-1 and MIP-2) play important roles in the inflammation induced by the intratracheal instillation of UFASs.
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PMID:Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. 1798 7

Integracions among T cells, B cells and macrophages is central to the immune response. These cells produce a number of biologically active proteins, which form complex network of cell-to-cell interaction, and regulate proliferation and function of the immune systems. Cytokines act on variety of cells type in a non-antigen specific manner. Only helper cells receive antigen specific signal and convert them via lymphokines secretion into antigen-nonspecific mediators of immune response. The followings cytokines have been found in asthamic airways: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alfa, GM-CSH. CD+4 cells are major source of cytokines in astmatic airway. It has been identified that two subsets of helper cells (TH-1 and TH-2) exist, which secret different cytokines profils. Both produce IL-1, IL-3, GM-CSF and TNF-alfa. TH-1 produce IL-2, IFN-gamma and TNF-beta (LT). TH-2 cells produce IL-4, IL-5 and IL-10. IL-4 produced by activited TH-2 subset, mast cells, and basophils is enhanced in asthma and responsible for IgE synthesis and expresion of IgE Fc-R-II. TH-1 specific IFN-gamma inhibits IL-4 induced IgE synthesis whereas TH-2 specific IL-10 supresses IFN-gamma secretion. IL-3, IL-4 and IL-5 stimulate the growth of mucosal mast cells and eosinophils. The presence of activated T cells and eosinophils in BAL-fluid as well as increased amount of IFN-gamma and slL-2R in circulation correlate with severity of disease. Interplay between T cells and inflammatory cells through the cytokines is crucial in regulating of inflammatory processes in allergic asthma.
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PMID:[Cytokines in bronchial asthma]. 1817 9

Systemic lupus erythematosus (SLE) is characterized by inflammatory and dysregulatory immune responses including overactive B cells, overproduction of proinflammatory cytokines, and T cell hyperactivity. PGE(2) modulates a variety of immune processes at sites of inflammation, including production of inflammatory cytokines. However, the role of PGE(2) in dysregulatory inflammatory and immune responses in lupus remains unclear. We investigated whether PGE(2) mediates production of inflammatory cytokines in pristane-induced lupus BALB/c mice. Our results showed that levels of serum and BAL PGE(2) and LPS-stimulated production of PGE(2) by peritoneal macrophages were remarkably increased in pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) enhanced production of IL-6, IL-10, and NO but decreased TNF-alpha by macrophages and augmented IFN-gamma, IL-6, and IL-10 by splenocytes from pristane-induced lupus mice compared to healthy controls. Exogenous PGE(2) also enhanced production of IFN-gamma, IL-6, and IL-10 by thymocytes from pristane-induced lupus mice. Indomethacin (Indo), a PGE(2) synthesis inhibitor, greatly inhibited LPS-induced production of IL-6 and IL-10 by macrophages from pristane-induced lupus mice, while enhanced TNF-alpha. Indo remarkably inhibited Con A-increased production of IFN-gamma, IL-6, and IL-10 by splenocytes and thymocytes from pristane-induced lupus mice. Therefore, our findings suggest that endogenous PGE(2) may mediate dysregulation of production of proinflammatory cytokines, such as IL-6, IL-10, and IFN-gamma, and NO in pristane-induced lupus mice.
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PMID:Prostaglandin E2-mediated dysregulation of proinflammatory cytokine production in pristane-induced lupus mice. 1844 9

Long-term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY-to-F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL-1 alpha, IL-1 beta, IL-6, IL-10, TNF-alpha and TGF-beta in BAL and of IL-1 alpha, IL-4 and GM-CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration-related injuries might improve outcomes in clinical lung transplantation.
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PMID:Chronic aspiration of gastric fluid induces the development of obliterative bronchiolitis in rat lung transplants. 1855 28

To determine the therapeutic potential of herbal medicine Moringa oleifera Lam. family: Moringaceae in the control of allergic diseases, the efficacy of the ethanolic extract of the seeds of the plant (MOEE) against ovalbumin (OVA)-induced airway inflammation in guinea pigs was examined. During the experimental period, the test drugs (MOEE or dexamethasone) were administered by oral route prior to challenge with aerosolized 0.5% OVA. Bronchoconstriction tests were performed and respiratory parameters (i.e., tidal volume and respiratory rate) were measured. At the end of experiment, blood was collected from each animal to perform total and differential counts and serum was used for assay of IL-4, IL-6, and TNFalpha. Lung lavage fluid (BAL) was collected for estimation of cellular content and cytokine levels. Lung tissue histamine assays were performed using the homogenate of one lobe from each animal; a separate lobe and the trachea were subjected to histopathology to measure the degree of any airway inflammation. The results suggest that in OVA-sensitized control animals that did not receive either drug, tidal volume (V(t)) was decreased, respiration rate (f) was increased, and both the total and differential cell counts in blood and BAL fluid were increased significantly. MOEE-treatment of sensitized hosts resulted in improvement in all parameters except BAL TNFalpha and IL-4. Moreover, MOEE-treatment also showed protection against acetylcholine-induced broncho-constriction and airway inflammation which was confirmed by histological observations. The results of these studies confirm the traditional claim for the usefulness of this herb in the treatment of allergic disorders like asthma.
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PMID:Effect of Moringa oleifera Lam. seed extract on ovalbumin-induced airway inflammation in guinea pigs. 1868 7

S1P has been demonstrated to protect against the formation of lipopolysaccharide (LPS)-induced lung edema when administered concomitantly with LPS. In the current study, we sought to determine the effectiveness of S1P to attenuate lung injury in a translationally relevant canine model of ALI when administered as rescue therapy. Secondarily, we examined whether the attenuation of LPS-induced physiologic lung injury after administration of S1P was, at least in part, caused by an alteration in local and/or systemic inflammatory cytokine expression. We examined 18, 1-year-old male beagles prospectively in which we instilled bacterial LPS (2-4 mg/kg) intratracheally followed in 1 h with intravenous S1P (85 microg/kg) or vehicle and 8 h of high-tidal-volume mechanical ventilation. S1P attenuated the formation of Q(s)/Q(t) (32%), and both the presence of protein (72%) and neutrophils (95%) in BAL fluid compared with vehicle controls. Although lung tissue inflammatory cytokine production was found to vary regionally throughout the LPS-injured lung, S1P did not alter the expression pattern. Similarly, BAL cytokine production was not altered significantly by intravenous S1P in this model. Interestingly, S1P potentiated the LPS-induced systemic production of 3 inflammatory cytokines, TNF-alpha (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction. In conclusion, intravenous S1P reduces inflammatory lung injury when administered as rescue therapy in our canine model of LPS-induced ALI. This improvement is observed in the absence of changes in local pulmonary inflammatory cytokine production and an augmentation of systemic inflammation.
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PMID:Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo. 1901 Feb 92

Titanium dioxide nanoparticles (TNP) are nanomaterials which have various applications including photocatalysts, cosmetics, and pharmaceuticals because of their high stability, anticorrosiveness, and photocatalytic properties. Induction of cytokines and potential chronic inflammation were investigated in mice treated with TNP (5 mg/kg, 20 mg/kg, and 50 mg/kg) by a single intratracheal instillation. Pro-inflammatory cytokines such as IL-1, TNF-a, and IL-6 were significantly induced in a dose-dependent manner at day 1 after instillation. The levels of Th1-type cytokines (IL-12 and IFN-gamma) and Th2-type cytokines (IL4, IL-5 and IL-10) were also elevated dose-dependently at day 1 and the inflammatory responses were sustained until the remainder of experimental period for 14 days. By the induction of Th2-type cytokines, the increased B cell distributions both in spleen and in blood, and increased IgE production in BAL fluid and serum were observed. In lung tissue, increase of inflammatory proteins (MIP and MCP) and granuloma formation were observed. Furthermore, the expressions of genes related with antigen presentation (H2-T23, H2-T17, H2-K1, and H2-Eb1) and genes related with the induction of chemotaxis of immune cells (Ccl7, Ccl3, Cxcl1, Ccl4, Ccl2) were markedly increased using microarray analysis. From these data, it could be suggested that TNP possibly cause chronic inflammatory diseases through Th2-mediated pathway in mice.
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PMID:Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. 1946 67


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