Top PDF Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

Levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR). ADMA levels in bronchoalveolar lavage fluid (BALF) and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM). Airway inflammation was assessed by bronchoalveolar lavage (BAL) total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS) signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses.
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1'-Acetoxychavicol acetate isolated from Alpinia galanga ameliorates ovalbumin-induced asthma in mice.

1'-Acetoxychavicol acetate isolated from Alpinia galanga ameliorates ovalbumin-induced asthma in mice.

The World Health Organization reports that 235 million people are currently affected by asthma. This disease is associated with an imbalance of Th1 and Th2 cells, which results in the upregulation of cytokines that promote chronic inflammation of the respiratory system. The inflammatory response causes airway obstruction and can ultimately result in death. In this study we evaluated the effect of 19-acetoxychavicol acetate (ACA) isolated from Alpinia galanga rhizomes in a mouse model of ovalbumin (OVA)-induced asthma. To generate the mouse model, BALB/c mice were sensitized by intraperitoneal injection of OVA and then challenged with OVA inhalation for 5 days. Mice in the vehicle control group were sensitized with OVA but not challenged with OVA. Treatment groups received dexamethasone, 25 mg/kg/day ACA, or 50 mg/kg/day ACA for 5 days. Asthma-related inflammation was assessed by bronchoalveolar lavage fluid cell counts and histopathological and immunohistochemical analysis of lung tissues. Our results showed that ACA reduced the infiltration of white blood cells (especially eosinophils) and the level of IgE in the lungs of mice challenged with OVA and suppressed histopathological changes such as airway remodeling, goblet-cell hyperplasia, eosinophil infiltration, and glycoprotein secretion. In addition, ACA inhibited expression of the Th2 cytokines interleukin (IL)-4 and IL-13, and Th1 cytokines IL-12a and interferon-c. Because asthmatic reactions are mediated by diverse immune and inflammatory pathways, ACA shows promise as an antiasthmatic drug candidate.
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Dendritic polyglycerolsulfate near infrared fluorescent (NIRF) dye conjugate for non-invasively monitoring of inflammation in an allergic asthma mouse model.

Dendritic polyglycerolsulfate near infrared fluorescent (NIRF) dye conjugate for non-invasively monitoring of inflammation in an allergic asthma mouse model.

Using a model of allergen-induced lung inflammation, we applied fluorescence imaging in combination with near-infrared (NIR) fluorescently-labeled dendritic polyglycerol sulfates (dPGS), a class of compounds that selectively bind to mediators of inflammatory processes such as L- and P-selectin and C3/C5 complement factors [14,15]. The role of selectin-ligand interac- tions in allergic asthma is well established, making them an attractive target for visualization of inflammation [16–19]. For example, reduced airway hyperresponsiveness in asthma in L- Selectin-deficient mice has been reported [19]. Furthermore, studies show that dPGS is transported into inflammatory cells e.g. in activated mononuclear cells [20,21]. Generally, dPGS consists of a highly branched (dendritic) polyglycerol core, which due to the large amount of hydroxyl end groups enables high functiona- lization. In our case, sulfate groups were generated from the hydroxyl groups, thereby creating the highly charged, polyanionic dPGS compound (Figure 1). dPGS acts via a multivalent binding mechanism mimicking naturally occurring selectin ligands [20], with a clearly demonstrated dependence of the binding affinity from molecular weight and degree of sulfation [15,21]. Sulfation of the hydroxyl groups in the polymer established a multivalent polyanionic entity with high affinity for L- and P-selectin [22]. Anti-inflammatory property of dPGS in much higher concentra- tions has been reported to occur as a result of a multivalent interaction enabled by the multitude of sulfate groups. For instance, binding of dPGS to L-selectin on leukocytes and P- selectin on inflamed vascular endothelium reduces leukocyte extravasation by shielding the adhesion molecule [22]. Addition- ally, inhibition of C5a generation inhibits leukocyte chemotaxis [14,22].
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Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-beta 1 and BMP-7

Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-beta 1 and BMP-7

Allergic asthma is characterized by chronic inflammation of the airways, bronchial hyper-responsiveness, and several structural changes in the lung, collectively termed airway remodeling [1,2]. It is a Th2-mediated inflammation that involves infiltration of effector T lymphocytes and eosinophils. Products of these cells’ activation and degranulation ultimately damage the parenchyma and degrade the extracellular matrix (ECM) components. During this injury, growth factors, which are primarily secreted in their inactive form, bind to the ECM and are released by proteolysis into their active form. TGF- b1 is one of these growth factors, being a key mediator of fibrosis [3,4]. TGF- b1 induces the differentiation of fibroblasts into myofibroblasts, which are the effector cells in many fibrotic lung diseases, including asthma [5]. The myofibroblast is characterized by expression of a-SMA, and by intensive synthesis of type I collagen, associated with increased proliferation, all key events in wound healing [6,7]. Specifically in asthma, the characteristic structural changes which occur in the lung are: thickening of the bronchial smooth muscle wall, high number of infiltrating cells, and deposition of an abnormal amount of ECM components beneath the bronchial epithelium. These alterations end up replacing the normal lung parenchyma by scar tissue, diminishing the gas exchange surface and, consequently, determining the decreased respiratory capacity of the patients. Although it has already been established that fibrosis is due to an
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An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

An extract of Crataegus pinnatifida fruit attenuates airway inflammation by modulation of matrix metalloproteinase-9 in ovalbumin induced asthma.

Total IgE, OVA-specific IgE and OVA-specific IgG1 were measured by enzyme-linked immunosorbent assay (ELISA). Briefly, 96-well microtiter plates were coated overnignt with isotype-specific coating (total IgE) and 10 m g/mL OVA in PBS- Tween 20 (OVA-specific IgE and OVA-specific IgG1). After washing and blocking of plate, samples were incubated for 2 hours. Subsequently, 96-well plates were washed, and HRP-conjugated goat anti-mouse IgE (total IgE and OVA specific IgE) and anti- mouse IgG1 antibody (OVA-specific IgG1) were added. After washing four times, 200 m L of o-phenylenediamine dihydrochlo- ride (Sigma-Aldrich, St. Louis, MO) was added to each well. The plate was incubated for 10 min in the dark and then absorbance was determined at 450 nm using a microplate ELISA reader (Bio- Rad Laboratories, CA, USA). Total IgE, OVA-specific IgE, and Figure 3. CPEE reduces mucus production in lung tissues of mice. (A) Histological examination of mucus secretion in lung tissue 48 h after the last OVA challenge. Lung tissue was fixed, sectioned at 4 mm thickness, and stained with periodic acid Schiff (PAS) for mucus production (magnification 6200). (B) Scoring of mucus production in lung sections were performed an image analyzer (Molecular Devices Inc., CA, USA). Quantitative analysis was assessed in at least four squares of a sample slide stained with PAS. NC; normal control mice treated with PBS only; OVA; OVA-sensitized/challenged mice; Mon; Montelukast (30 mg/kg) + OVA-sensitized/challenged mice; CPEE-1; CPEE (100 mg/kg) + OVA-sensitized/ challenged mice; CPEE-2; CPEE (200 mg/kg) + OVA-sensitized/challenged mice. Values are expressed as mean 6 SD (n = 6/group). *Significantly different from NC, P,0.05; {significantly different from OVA, P,0.05.
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Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma.

Concomitant exposure to ovalbumin and endotoxin augments airway inflammation but not airway hyperresponsiveness in a murine model of asthma.

We assessed the CD4+ T cell numbers and CD4+CD25+ FoxP3+ cells in the lungs of animals undergoing three OVA challenges. Following the assessment of methacholine responsive- ness and BALF collection, the right lung of each animal was excised and placed in cold RPMI-1640 medium, containing 8% heat-inactivated FBS, 2 mM L-glutamine, 50 mg/ml gentamycin and 10 mM HEPES (Invitrogen, USA.). The lung was removed from the medium and transferred to a dish containing 4 ml of sterile DPBS (Invitrogen) supplemented with collagenase (0.2 Wunsch units/ml, Clostridium histolyticum, Type XI-S, Sigma), DNAse I (1000 DNase units/ml, Type II-S, Sigma) and 0.5 mM calcium. The lung was also inflated with 1 ml of the same solution, minced with forceps and a scalpel blade and incubated on an orbital shaker at 37 uC for 1 hour. The reaction was stopped with 5 ml cold RPMI-1640 medium (as above) with 2 mM EDTA (Invitrogen,) and 50 mM b-mercaptoethanol (Sigma). The lung tissues were mechanically disrupted, passed through 70 mm and 40 mm BD Falcon cell strainers and finally centrifuged at 1500 rpm for 5 min. Red blood cells were lysed with ammonium chloride and leukocytes were counted using a Beckman Coulter A c .T Counter. Cells were incubated with mouse BD Fc Block (BD Biosciences, Canada), then stained with FITC-conjugated rat anti- mouse CD4 mAb (clone H129.19), followed by PE CD25 (clone PC61), or the appropriate isotype control Ab (BD). Cells were then fixed with BD Cytofix/Cytoperm solution, incubated with 1% BSA in BD Perm/Wash solution and finally stained with APC Foxp3 mAb (clone FJK-16s) or isotype control Ab (eBioscience, San Diego, CA, USA). 50000 events were acquired for each condition using the BD FacsCalibur (Becton Dickinson). Cells were gated first based on CD4-positivity (vs side scatter) and then based on forward scatter (vs side scatter) to exclude debris or small dead cells.
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The effects of overexpression of histamine releasing factor (HRF) in a transgenic mouse model.

The effects of overexpression of histamine releasing factor (HRF) in a transgenic mouse model.

Cytokine levels. Asthma is a chronic inflammatory disorder of the lung and TH2 inflammation of the airway is a major component of asthma. It has been demonstrated in animal models of asthma that allergens can elicit TH2 inflammation and that IL- 4 is essential in this response. For example, in the presence of IL-4, naı¨ve CD4+ T cells differentiate into TH2 cells [31]. In order to investigate the underlying molecular mechanism of the augmented pulmonary inflammation in the HRF-inducible transgenic mouse we investigated several cytokine and chemokine expression profiles in the lung. As shown in Figure 10, when mice were sensitized and challenged with OVA, transgene++ (++/OVA) mice had greater mRNA levels of IL-4 (p = 0.04) than CC10 littermate controls treated the same way (CC10/OVA). There were no differences observed in mRNA levels for eotaxin, IL-5 or IL-13 between these groups (Figure 10). Protein levels for IL-4 were also measured from BAL supernatants (Figure 10 Panel B). IL-4 protein levels were Figure 4. Transgenic Protein Expression for Mice in Protocol II. Panel A depicts the relative amount of HRF protein based on densitometric analysis of Western blots. Panel B is the relative amount of GFP protein based on Western blots. Relative protein levels are expressed as a function of the positive control of each protein. In all cases mice were sensitized with PBS or OVA, then all mice were challenged with OVA. Each group had between 6 and 9 mice (backcrosses 3–6).
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Correction: G-Protein-Coupled Estrogen Receptor Agonist Suppresses Airway Inflammation in a Mouse Model of Asthma through IL-10.

Correction: G-Protein-Coupled Estrogen Receptor Agonist Suppresses Airway Inflammation in a Mouse Model of Asthma through IL-10.

In the Materials and Methods section, there is an error in the fifth and sixth sentences of the section titled “Flow cytometry.” This sentence should read: 2), PE-Cy5-conjugated anti-TCRβ (BioLegend, San Diego, CA), PE-Cy7-conjugated ant-NK1.1 (BioLegend), PE-Cy7-conjugated anti-CD8a (BioLegend), PE-CF594-conjugated anti-CD4 (BD Biosciences), and GPR30 (N- 15)-R Antibody (Santa Cruz Biotechnology, Santa Cruz, CA) with subsequent staining by Alexa Fluor 488-conjugated goat anti-rabbit immunoglobulin G (IgG) (Invitrogen, Grand Island, NY). Then, the cells were washed, permeabilized with BD Cytofix/Cytoperm (BD Bio- sciences), and stained with PE-conjugated anti-IL-10 (BioLegend) to detect intracellular IL-10.
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Effects of a silenced gene in Boolean network models

Effects of a silenced gene in Boolean network models

It is very crucial impression of modeling the qualitative behavior of biological networks where molecules are represented as nodes and the molecular interactions are so called edges (Din, 2014; Zhang, 2012, 2015, 2016a, 2016b). Thus, investigation of gene silencing requires that an appropriate gene regulatory network model should be selected. Gene regulatory network models are mainly categorized into three groups namely, logical models, continuous models and single-molecule models. Those that fall into logical category are discrete models so that they can explain the existing network qualitatively, allowing a basic knowledge of the dynamics and functions of a network under different conditions (Bolouri and Davidson, 2002). Their applicability covers a wide range of systems including biological phenomena, one of which is the Boolean modeling technique introduced by Kauffman (Glass and Kauffman, 1973; Kauffman, 1993). Under the Boolean model, the state of the genes, which are Boolean variables and the phenotypic transitions which they can make are determined by the states of the other genes in the network with the Boolean logic functions governing each gene (Albert, 2004). One of the aspects of all Boolean model is that microarray experiments must first be processed to binary in the experimental data from time series as the Boolean functions of the networks can only process binary data (Hakamada et al., 2001). Successfully applied to several different organisms, Boolean GRN models are a simple and useful model to describe genetic regulatory systems (Hickman and Hodgman, 2009).
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RW Egan+ , D Athwahl, C-C Chou, RW Chapman, S Emtage, C-H Jenh, TT Kung, PJ Mauser, NJ Murgolo, MW Bodmer

RW Egan+ , D Athwahl, C-C Chou, RW Chapman, S Emtage, C-H Jenh, TT Kung, PJ Mauser, NJ Murgolo, MW Bodmer

In our monkey model of asthma, adult cyno- molgus monkeys were tranquilized with ketamine, injected intravenously with the antibody of choice, anesthetized and intubated with an endotracheal tube through which we inserted a pediatric bron- choscope in order to conduct broncheoaveolar la- vage with two 10 ml saline washes (Mauser et al. 1995). At the same time, we evaluated the respon- siveness of the lungs to a dose response of aerosol histamine. These monkeys were naturally sensi- tive to aerosol Ascaris antigen, which was used as the allergic stimulus. Twenty-four hour later, bronchoalveolar lavage and airway hyperreactiv- ity were evaluated again such that each monkey served as its own control. In a set of six monkeys, airway hyperreactivity and bronchoalveolar lavage eosinophils were measured in the absence of the antibody. Two weeks later, when the pulmonary parameters in this set of monkeys had returned to baseline, the experiment was repeated in the pres- ence of the antibody, such that this set of monkeys was internally controlled.
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Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model.

Although with embedded study, the immune-modulatory effect of microbial metabolites is gradually known or accepted, owing to the multiplicity and complexity of diet-microbiota- immune system, the current understandings are still insufficient to explain completely the underlying mechanisms, remaining unknown about the interaction. But another equally intriguing finding emerged from the study is that insoluble-fiber cellulose, poorly fermented by gut bacteria, also exhibits a strong prevention and inhibiting effect of allergic airway inflamma- tion. Apparently, it is likely to need other pathways to further explain these potential influences of fiber-diet. By the comparative analysis of the microbial colony structure among the groups, our study noted that similar to the role of readily fermentable pectin, poorly fermentable cellu- lose significantly improved the structure of intestinal flora by increasing relative ratio of Bacter- oidetes to Firmicutes, as well as increased the count of common probiotic bacteria such as Lactobacillus and Bifidobacteriumare. Interestingly, Bacteroidetes bacteria are major producers of SCFAs and the increased ratio of Bacteroidetes to Firmicutes has also been observed in mice exposed to Western high-fat diets [9,13,36,37,38]. In addition, Lactobacillus and Bifidobacter- iumare, as typical probiotic bacteria, enable the homeostasis of immune cells and decrease the susceptibility to allergic inflammation, well-supported by a mounting body of evidences [10,11,39–44]. Furthermore, the beneficial effect of E. coli against allergic diseases has also been confirmed in other animal studies [26,45–46]. As Maslowski [35] argued, if diet affects the composition of microbiota, and the microbiota regulates immune and inflammatory responses, then diet changes should have easily quantifiable effects on the immune response. For these reasons, the protection of cellulose against AAD maybe more dependent on the direct interactions of microbiota-immune system influenced by fiber-induced variations in Gut microbacteria. The inconsistent protection mechanisms need to be investigated further.
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Roughness of surface of vacuum castings prepared in plaster moulds

Roughness of surface of vacuum castings prepared in plaster moulds

Results of measurements are presented in table 2 and 3. Examples of profilograms from the surface of bronze CuSn10 casting made in Gold Star XL plaster mould are presented in Figure 6. Analysis of the test results did not revealed a clear dependences between surface roughness of castings and methods of the preparation. Roughness values are random, independent on casting temperature and temperature and material of the molds. The one regularity that could be observed was that lower roughness parameter Ra showed test casts made of aluminum alloy AlSi11, next bronze casts CuSn10 and the higher value was observed for CuSn5Zn5Pb5 bronze.
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Pregnancy in Chronic Arthritis: Only a Matter of Planning

Pregnancy in Chronic Arthritis: Only a Matter of Planning

Chronic arthritis often afects women of childbearing age. The old concept that having chronic arthritis constitutes a major obstacle to women when planning a pregnancy is now obsolete. Thanks to our current capacity to control the activity of rheumatoid arthritis and other chronic inlammatory conditions, and due to the availability of highly efective drugs such as tumour necrosis factor inhibitor agents and other biological agents, many women with these diseases are now able to consider the challenge of childbearing and raising children. Careful pre-conceptional evaluation and risk assessment constitutes the irst step of proper care, which can be individualised according to the disease. More than ever, rheumatologists must know how to deal with this situation, and must be able to provide adequate counselling regarding the control of arthritis during conception and pregnancy.
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Evaluation of susceptibility of the ZRE1 alloy to hot cracking in conditions of forced strain

Evaluation of susceptibility of the ZRE1 alloy to hot cracking in conditions of forced strain

In order to evaluate the susceptibility to hot cracking in the high-temperature brittleness range, we have determined the changes of temperature of individual points when the alloy was cooled down from the solidus temperature. The tests were performed on the cylindrical Ø 10 x 120 mm specimens, using the Gleeble 3800 simulator, at Iron Metallurgy Institute in Gliwice. Four S-type thermocouples were pressure welded to the specimens: in the specimen axis and 2, 5 and 8 mm away from the axis. The specimens were fixed in copper holders, keeping a constant distance of 33 mm, and then were heated in the argon atmosphere at the 20 0 C/s rate to the temperature of liquid phase appearance, and were afterwards freely cooled. Changes in
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J. bras. pneumol.  vol.34 número11 en v34n11a05

J. bras. pneumol. vol.34 número11 en v34n11a05

Objective: To evaluate the usefulness of determining the inflammatory component of airway diseases (inflammometry) by induced sputum cell counts, as well as its influence on treatment decisions in a tertiary facility for the treatment of respiratory diseases. Methods: We analyzed 151 sputum samples from 132 consecutive patients referred for clinical sputum induction by five pulmonologists between July of 2006 and February of 2007. A structured questionnaire related to the reasons for requesting the test and to the therapeutic decision making based on test results was completed by each attending physician upon receiving the test results. Induced sputum was obtained and processed according to a technique previously described. Results: The principal motives for ordering the test were inhaled corticosteroid dose titration in patients with moderate-to-severe asthma (in 54.3%), investigation of chronic cough (in 30.5%), and monitoring airway inflam- mation in patients with bronchiectasis (in 7.3%) or chronic obstructive pulmonary disease (in 6%). Of the 82 patients with asthma, 47 (57%) presented eosinophilic bronchitis (>3% eosinophils). Nonasthmatic eosinophilic bronchitis was diagnosed in 9 (19%) of the 46 patients with chronic cough. Neutrophilic bronchitis (>65% neutrophils) was found in 13 patients, of which 5 had asthma, 2 had chronic cough, and 6 had chronic obstructive pulmonary disease/bronchiectasis. Based on the induced sputum results, the corticosteroid dose was modified in 48 asthma patients (64.7%). Conclusions: The systematic application of inflammometry using induced sputum cell counts can be beneficial for patients with airway diseases, particularly those with asthma or chronic cough.
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Prostatic inflammation induces fibrosis in a mouse model of chronic bacterial infection.

Prostatic inflammation induces fibrosis in a mouse model of chronic bacterial infection.

The inflammatory infiltrates present in the VP, DLP, and AP were characterized 28 days after bacterial inoculation. CD3+ T cells (Figure 5A), CD20+ B cells (Figure 5B) and F4/80+ macrophages (Figure 5C) were the predominant inflammatory cells found in all three E. coli infected prostatic lobes. A relatively small but significant number of neutrophils were also present (Figure 5D). To determine the cell type responsible for collagen synthesis associated with inflammation we performed immunohis- tochemical costaining 7 days post-instillation, a time point that corresponds to the peak of 3 H-hydroxyproline incorporation in the inflamed prostate. Staining for vimentin and a-smooth muscle actin surprisingly showed no evidence of VIM+aSMA+ myofi- broblasts in either the saline instilled or E. coli infected prostates (Figure S3). In contrast, staining for vimentin and CD45 showed abundant number of CD45+VIM+ fibrocytes in the E. coli infected prostates while only minimal number of fibrocytes was detected in the saline instilled prostates (Figure 6A–B). To determine if these fibrocytes are involved in collagen synthesis we performed staining for prolyl 4-hydroxylase (P4H), a key enzyme involved in collagen synthesis that catalyzes the conversion of proline to hydroxyproline before collagen secretion. Triple immunohistochemical staining for vimentin, CD45 and P4H in the E. coli infected prostates demonstrated P4H expression in a subpopulation of CD45+VIM+ fibrocytes (Figure 6C–D). Further assessment of prostatic cells isolated from saline instilled and E. coli infected mice using flow cytometry demonstrated that CD45+VIM+ fibrocytes are present within collagen type I (COL1) positive cells. Consistent with our immunohistochemical finding, there was a 6-fold increase in the percentage of CD45+VIM+ fibrocytes enriched in COL1 expressing cell population from the E. coli infected prostates (Figure 7). This observation strongly suggests fibrocytes as collagen-producing cells in chronic bacterial-induced prostatic inflammation.
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Eosinophilic inflammation in allergic asthma

Eosinophilic inflammation in allergic asthma

Airway remodeling is the cellular and structural changes in the airways, mainly resulting from repair processes in response to persistent inflammation, and that contribute to irreversibility of lung functions observed in asthma patients, including airway dys- function and clinical symptoms observed in allergic asthma (Vig- nola et al., 2000, 2003; Phipps et al., 2004; Fattouh and Jordana, 2008). Among structural changes can be noted subepithelial fibro- sis, smooth muscle hypertrophy/hyperplasia, epithelial cell mucus metaplasia, and increased angiogenesis (Aceves and Broide, 2008). Eosinophils seem to contribute to airway remodeling in several ways, including through release of eosinophil-derived mediators such as transforming growth factor (TGF)-β, secretion of cationic proteins, and cytokines, as well as through interactions with mast cell and epithelial cells. Many of these factors can directly acti- vate epithelium and mesenchymal cells, deeply related to the development of airway remodeling (Kariyawasam and Robinson, 2007; Aceves and Broide, 2008; Venge, 2010). Eosinophil-derived cytokines are in the modulation of Th2 responses that trigger macrophage production of TGF-β 1 , which serves as a stimulus for
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TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma.

TCDD-Induced Activation of Aryl Hydrocarbon Receptor Inhibits Th17 Polarization and Regulates Non-Eosinophilic Airway Inflammation in Asthma.

The AhR is expressed in lung tissue [21, 22], and AhR activation plays a key role in the inflam- matory reaction [17]. Thus, we investigated the regulatory function of TCDD in non-eosino- philic airway inflammation. Six-wk-old mice were intranasally sensitized with OVA and LPS, and TCDD was gavaged one day prior to being sensitized and challenged. The lung histology was analyzed via HE or PAS staining. As shown in Fig 2A and 2B, the inflammatory cells and mucus production were not significantly different in the lungs between the control and TCDD alone groups. However, these variables were substantially decreased in the lungs from the TCDD-treatment OVA/LPS sensitized mice compared with the non-treatment mice. Further- more, we analyzed the neutrophil infiltration in the lungs by MPO and Gr-1 staining. As shown in Fig 2C and 2D, the neutrophil infiltration was also significantly decreased in the lungs from the TCDD-treatment OVA/LPS sensitized mice compared with the non-treatment mice. A quantitative analysis indicated the same results (Fig 2E). Through an analysis of the cellular composition in BALF, we determined that eosinophils and neutrophils were both sig- nificantly decreased in the TCDD-treatment group compared with the non-treatment group (Fig 3A and 3B). When challenged with various concentrations of methacholine, the RL was significantly decreased, whereas the Cdyn was significantly increased in the TCDD-treatment group compared with the non-treatment group (Fig 3C). Taken together, these findings suggest that TCDD-induced AhR activation prevents the development of allergen-induced non-eosin- ophilic airway inflammation and airway hyperresponsiveness.
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Analysis of quality and cost of FeSiMg treatment master alloy vs. cored wire in production of ductile cast iron

Analysis of quality and cost of FeSiMg treatment master alloy vs. cored wire in production of ductile cast iron

At the Foundrys of Drawski M łyn and “WSK–Rzeszów” Metallurgical Plant in Rzeszów, a special technique of the nodularising (or vermicularising ) treatment was implemented. It was based on the use of cored wires, one cored with magnesium, and another with inoculant.

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Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.

Role of CD14 in a mouse model of acute lung inflammation induced by different lipopolysaccharide chemotypes.

Effects of sCD14 on S-LPS induced lung inflammation The data presented above provided clear evidence for a bimodal role of CD14 in the pulmonary responses induced by S-LPS. Since sCD14 can modulate LPS-induced responses [7], we were interested in establishing whether sCD14 can compensate for CD14 gene deficiency with regard to inhibition and enhancement of S-LPS effects at different doses. First, we measured sCD14 concentrations in BALF of WT mice 6 hours after instillation of different doses of S-LPS (10, 1 and 0.1 m g). As shown in figure 4, S- LPS elicited a dose-dependent rise in BALF sCD14 levels. To exclude the possibility that the increase in alveolar sCD14 levels resulted from leakage of serum proteins, total protein concentrations in BALF of LPS-treated WT mice were assessed. No differences in total BALF protein levels were observed in these mice 6 hours after treatment with 10, 1 or 0.1 m g S-LPS (data not shown). Next, we administered CD14KO mice with sCD14 (10 m g) intranasally together with S-LPS at either 10 m g (i.e. a dose at which CD14 inhibits S-LPS induced lung inflammation, Fig. 2) or 0.1 m g (i.e. a dose at which CD14 enhances S-LPS induced lung inflammation, Fig. 2). In these experiments the phenotype of CD14KO mice after intranasal administration of S-LPS at a high or low dose was reproduced (Fig. 5). Importantly, sCD14 treatment partially reversed the phenotype of CD14KO mice at both S-LPS doses. Specifically, whereas sCD14 did not impact on the enhanced PMN influx in CD14KO mice upon instillation of S-LPS at 10 m g (Fig. 5A), sCD14 reduced the exaggerated TNF release in CD14 KO mice to levels found in WT mice (P,0.01 for the difference with CD14 KO, Fig. 5C). At this LPS dose, neither sCD14 administration nor CD14 deficiency influenced LIX release. In addition, whereas sCD14 modestly but significantly increased the reduced PMN influx in CD14 KO mice upon instillation of S-LPS at 0.1 m g (P,0.01 for the difference with CD14 KO mice, Fig. 5B), this treatment did not influence the reduced TNF release into BALF in CD14 KO mice at this LPS dose (Fig. 5D). Remarkably, however, sCD14 administration strongly increased the release of LIX in CD14KO mice exposed to 0.1 m g S-LPS (P ,0.001 versus CD14KO mice, Fig. 5F). Taken together, these results suggest that sCD14 may inhibit or facilitate S-LPS effects in the bronchoalveolar space depending on the LPS dose used.
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