ovalbumin and Hypertrophy

Studies suggest that exercise can improve vaccination responses in humans. Chronic stress can lead to immunosuppression, and there may be a role for exercise in augmenting immune responses.. To investigate the effects of acute eccentric exercise (ECC) and voluntary wheel exercise training (VWR) on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. We hypothesized that both ECC and VWR would attenuate chronic stress-induced reductions in vaccination responses.. Mice were randomized into four groups: control (CON), stress (S)-ECC, S-VWR, and S-sedentary (SED). Stressed groups received chronic restraint stress for 6 h·d, 5 d·wk for 3 wk. After the first week of stress, S-ECC were exercised at 17 m·min speed at -20% grade for 45 min on a treadmill and then intramuscularly injected with 100 μg of ovalbumin (OVA) and 200 μg of alum adjuvant. All other groups were also vaccinated at this time. Stress-VWR mice voluntarily ran on a wheel for the entire experiment. Plasma was collected before, and at 1, 2, and 4 wk postvaccination. Enzyme-linked immunosorbent assay was performed to analyze anti-OVA IgG and IgM antibodies. After 3 wk of chronic stress, all mice were injected with OVA into the ear to determine the delayed-type hypersensitivity.. We found that chronic restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found both S-ECC and S-VWR groups had significantly elevated anti-OVA IgG (P < 0.05), whereas no significant differences between the two exercise groups. Neither S-ECC nor S-VWR altered anti-OVA IgM or delayed-type hypersensitivity responses compared with S-SED group.. Acute eccentric exercise and voluntary exercise training alleviated the chronic stress-induced anti-OVA IgG reductions in vaccination responses.

Topics: Adrenal Glands; Animals; Hypertrophy; Immunity, Cellular; Immunoglobulin G; Immunoglobulin M; Male; Mice, Inbred C57BL; Models, Animal; Organ Size; Ovalbumin; Physical Conditioning, Animal; Random Allocation; Spleen; Stress, Psychological; Vaccination; Weight Loss

Upregulation of WISP1 has been demonstrated in lung remodeling. Moreover, it has been recently found that some signaling components of WNT pathway can activate GSK3β signaling to mediate remodeling of airway smooth muscle (ASM) in asthma. Therefore, we hypothesized that WISP1, a signaling molecule downstream of the WNT signaling pathway, is involved in PI3K/GSK3β signaling to mediate ASM remodeling in asthma. Our results showed that WISP1 depletion partly suppressed OVA-induced ASM hypertrophy in vivo. In vitro, WISP1 could induce hBSMC hypertrophy and proliferation, accompanied by upregulation of levels of PI3K, p-Akt, p-GSK3β, and its own expression. TGF-β treatment could increase expression of PI3K, p-Akt, p-GSK3β, and WISP1. SH-5 treatment could partly suppress TGF-β-induced hypertrophy and proliferation of hBSMC, and depress expression of p-GSK3β and WISP1. In conclusion, WISP1 may be a potential inducer of ASM proliferation and hypertrophy in asthma. The pro-remodeling effect of WISP1 is likely due to be involved in PI3K-GSK3β-dependent noncanonical TGF-β signaling.

Topics: Airway Remodeling; Animals; Asthma; Bronchi; CCN Intercellular Signaling Proteins; Cell Line; Cell Movement; Cell Proliferation; Glycogen Synthase Kinase 3 beta; Humans; Hyperplasia; Hypertrophy; Male; Myocytes, Smooth Muscle; Ovalbumin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta

This study aimed to explore the effects of curcumin on experimental allergic rhinitis in rats.. Twenty-eight male Wistar albino rats were randomly divided into four groups: a control group; a group in which allergic rhinitis was induced and no treatment given; a group in which allergic rhinitis was induced followed by treatment with azelastine hydrochloride on days 21-28; and a group in which allergic rhinitis was induced followed by treatment with curcumin on days 21-28. Allergy symptoms and histopathological features of the nasal mucosa were examined.. The sneezing and nasal congestion scores were higher in the azelastine and curcumin treatment groups than in the control group. Histopathological examination showed focal goblet cell metaplasia on the epithelial surface in the azelastine group. In the curcumin group, there was a decrease in goblet cell metaplasia in the epithelium, decreased inflammatory cell infiltration and vascular proliferation in the lamina propria.. Curcumin is an effective treatment for experimentally induced allergic rhinitis in rats.

Topics: Administration, Intranasal; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Chondrocytes; Cilia; Curcumin; Eosinophils; Goblet Cells; Hyperemia; Hypertrophy; Male; Mast Cells; Metaplasia; Nasal Mucosa; Ovalbumin; Phthalazines; Random Allocation; Rats; Rats, Wistar; Rhinitis, Allergic; Sneezing

The increase of airway smooth muscle (ASM) mass in asthma results from hypertrophic and hyperplastic stimuli, and leads to an increase in cellular contractile proteins. However, little evidence correlates the relative contributions of hypertrophic and hyperplastic muscle with functional effects on airway resistance. We performed a ventilator-based assessment of respiratory mechanics and responsiveness to methacholine in a murine model of acute (3-week) ovalbumin (OVA)-induced airway inflammation, compared with a chronic (12-week) model. We correlated functional changes in airways Newtonian resistance (RN), peripheral tissue damping (G), and elastance (H) with the relative contributions of proliferation, hypertrophy, and apoptosis to increased ASM mass. Immunohistochemical analyses of treated (OVA-sensitized and OVA-challenged; OVA/OVA) and control (OVA-sensitized and saline-challenged; OVA/PBS) murine lungs showed an increase in ASM area in chronic, but not acute, OVA/OVA-treated mice that correlated positively with increased airway resistance to methacholine. Acute OVA/OVA-treated ASM exhibited an increase in proliferation with diminished apoptosis, which resolved in the chronic OVA/OVA model. Chronic OVA/OVA-treated ASM exhibited hypertrophy. Distinct temporal differences exist in the response of murine airways to antigenic challenge. We report that ASM proliferation and diminished apoptosis occur during the acute phase, followed by the development of smooth muscle hypertrophy and an increased muscle mass with chronic challenge, that correlate strongly with increased airway Newtonian resistance. The identification of a functionally relevant hypertrophic bronchial muscle mass highlights the possibility of regulating airway muscle hypertrophy as a novel therapeutic target in asthma.

Topics: Airway Resistance; Animals; Apoptosis; Asthma; Cell Proliferation; Disease Models, Animal; Female; Hypertrophy; Methacholine Chloride; Mice; Mice, Inbred BALB C; Muscle, Smooth; Ovalbumin; Respiratory Hypersensitivity

We examined the contribution of p70 ribosomal S6 kinase (p70S6K) to airway smooth muscle hypertrophy, a structural change found in asthma. In human airway smooth muscle cells, transforming growth factor (TGF)-beta, endothelin-1, and cardiotrophin-1 each induced phosphorylation of p70S6K and ribosomal protein S6 while increasing cell size, total protein synthesis, and relative protein abundance of alpha-smooth muscle actin and SM22. Transfection of myocytes with siRNA against either p70S6K or S6, or infection with retrovirus encoding a kinase-dead p70S6K, reduced cell size and protein synthesis but had no effect on contractile protein expression per mg total protein. Infection with a retrovirus encoding a constitutively active, rapamycin-resistant (RR) p70S6K increased cell size but not contractile protein expression. siRNA against S6 decreased cell size in myocytes expressing RR p70S6K. Finally, TGF-beta treatment, but not RR p70S6K expression, increased KCl-induced fractional shortening. Together, these data suggest that p70S6K activation is both required and sufficient for airway smooth muscle cell size enlargement but not contractile protein expression. Further, ribosomal protein S6 is required for p70S6K-mediated cell enlargement. Finally, we have shown for the first time in a functional cell system that p70S6K-mediated myocyte enlargement alone, without preferential contractile protein expression, is insufficient for increased cell shortening.

Topics: Airway Remodeling; Animals; Asthma; Cell Enlargement; Cells, Cultured; Contractile Proteins; Cytokines; Disease Models, Animal; Endothelin-1; Enzyme Activation; Humans; Hypertrophy; Lung; Mice; Mice, Inbred BALB C; Microfilament Proteins; Muscle Contraction; Muscle Proteins; Muscle, Smooth; Mutation; Myocytes, Smooth Muscle; Ovalbumin; Phenotype; Phosphorylation; Potassium Chloride; Ribosomal Protein S6; Ribosomal Protein S6 Kinases, 70-kDa; RNA Interference; Transduction, Genetic; Transforming Growth Factor beta

Increased airway smooth muscle (ASM) mass, a characteristic finding in asthma, may be caused by hyperplasia or hypertrophy. Cell growth requires increased translation of contractile apparatus mRNA, which is controlled, in part, by glycogen synthase kinase (GSK)-3beta, a constitutively active kinase that inhibits eukaryotic initiation factor-2 activity and binding of methionyl tRNA to the ribosome. Phosphorylation of GSK-3beta inactivates it, enhancing translation. We sought to quantify the contributions of hyperplasia and hypertrophy to increased ASM mass in ovalbumin (OVA)-sensitized and -challenged BALB/c mice and the role of GSK-3beta in this process. Immunofluorescent probes, confocal microscopy, and stereological methods were used to analyze the number and volume of cells expressing alpha-smooth muscle actin and phospho-Ser(9) GSK-3beta (pGSK). OVA treatment caused a 3-fold increase in ASM fractional unit volume or volume density (Vv) (PBS, 0.006 +/- 0.0003; OVA, 0.014 +/- 0.001), a 1.5-fold increase in ASM number per unit volume (Nv), and a 59% increase in volume per cell (Vv/Nv) (PBS, 824 +/- 76 microm(3); OVA, 1,310 +/- 183 mum(3)). In OVA-treated mice, there was a 12-fold increase in the Vv of pGSK (+) ASM, a 5-fold increase in the Nv of pGSK (+) ASM, and a 1.6-fold increase in Vv/Nv. Lung homogenates from OVA-treated mice showed increased GSK-3beta phosphorylation and lower GSK-3beta activity. Both hyperplasia and hypertrophy are responsible for increased ASM mass in OVA-treated mice. Phosphorylation and inactivation of GSK-3beta are associated with ASM hypertrophy, suggesting that this kinase may play a role in asthmatic airway remodeling.

Topics: Actins; Animals; Asthma; Cell Size; Flow Cytometry; Fluorescent Antibody Technique; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hyperplasia; Hypertrophy; Immunoblotting; Immunoprecipitation; Lung; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Microscopy, Fluorescence; Muscle, Smooth; Ovalbumin; Phosphorylation; Pneumonia; Respiratory System; Transforming Growth Factor beta

Asthma is a heterogeneous disease that has been increasing in incidence throughout western societies and cytokines, including proinflammatory tumour necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of asthma. Anti-TNF-alpha therapies have been established successfully in the clinic for diseases such as rheumatoid arthritis and Crohn's disease. TNF-alpha-blocking strategies are now being trialled in asthma; however, their mode of action is poorly understood. Based on the observation that TNF-alpha induces lymph node hypertrophy we have attempted to investigate this as a mechanism of action of TNF-alpha in airway inflammation by employing two models of murine airway inflammation, that we have termed short and long models, representing severe and mild/moderate asthma, respectively. The models differ by their immunization schedules. In the short model, characterized by eosinophilic and neutrophilic airway inflammation the effect of TNF-alpha blockade was a reduction in draining lymph node (DLN) hypertrophy, eosinophilia, interleukin (IL)-5 production and immunoglobulin E (IgE) production. In the long model, characterized by eosinophilic inflammation, TNF-alpha blockade produced a reduction in DLN hypertrophy and IL-5 production but had limited effects on eosinophilia and IgE production. These results indicate that anti-TNF-alpha can suppress DLN hypertrophy and decrease airway inflammation. Further investigations showed that anti-TNF-alpha-induced inhibition of DLN hypertrophy cannot be explained by preventing l-selectin-dependent capture of lymphocytes into the DLN. Given that overall TNF blockade was able to suppress the short model (severe) more effectively than the long model (mild/moderate), the results suggest that TNF-alpha blocking therapies may be more effective in the treatment of severe asthma.

Topics: Adoptive Transfer; Animals; Asthma; Bronchial Hyperreactivity; Cytokines; Eosinophilia; Etanercept; Flow Cytometry; Hypertrophy; Immunoglobulin G; Lung; Lymph Nodes; Mice; Mice, Inbred BALB C; Models, Animal; Ovalbumin; Receptors, Tumor Necrosis Factor; T-Lymphocytes; Time; Tumor Necrosis Factor-alpha

We developed a model of severe allergic inflammation and investigated the impact of airway and lung parenchyma remodelling on in vivo and in vitro respiratory mechanics. BALB/c mice were sensitized and challenged with ovalbumin in severe allergic inflammation (SA) group. The control group (C) received saline using the same protocol. Light and electron microscopy showed eosinophil and neutrophil infiltration and fibrosis in airway and lung parenchyma, mucus gland hyperplasia, and airway smooth muscle hypertrophy and hyperplasia in SA group. These morphological changes led to in vivo (resistive and viscoelastic pressures, and static elastance) and in vitro (tissue elastance and resistance) lung mechanical alterations. Airway responsiveness to methacholine was markedly enhanced in SA as compared with C group. Additionally, IL-4, IL-5, and IL-13 levels in the bronchoalveolar lavage fluid were higher in SA group. In conclusion, this model of severe allergic lung inflammation enabled us to directly assess the role of airway and lung parenchyma inflammation and remodelling on respiratory mechanics.

Topics: Animals; Asthma; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperplasia; Hypertrophy; Methacholine Chloride; Mice; Mice, Inbred BALB C; Microscopy, Electron; Muscarinic Agonists; Muscle, Smooth; Ovalbumin; Pulmonary Alveoli; Pulmonary Eosinophilia; Respiratory Hypersensitivity; Respiratory Mechanics

Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining is a widely accepted method for the detection of DNA fragmentation in nuclei of apoptotic cells. Tumor necrosis factor (TNF)-alpha is closely associated with changes in condylar cartilage and modulates apoptosis in various tissues including cartilage. The aim of this study was to investigate the relationship between apoptotic chondrocytes and TNF-alpha in a rabbit model of arthritis.. Unilateral temporomandibular joint (TMJ) arthritis was induced in 20 adult New Zealand White rabbits. From 1 day to 6 weeks after the induction of arthritis, immunohistochemical analysis for TNF-alpha and TUNEL was performed.. In condylar cartilage, TNF-alpha-positive cells and TUNEL-positive cells were localized together. TNF-alpha-positive chondrocytes seemed to precede TUNEL-positive cells.. The results of the present study suggest that TNF-alpha may be involved in apoptosis and/or apoptotic necrosis of chondrocytes as TMJ arthritis progresses from the acute to chronic stage.

Topics: Animals; Antigens; Apoptosis; Arthritis, Experimental; Cartilage; Cell Nucleus; Cell Proliferation; Chondrocytes; Disease Models, Animal; Disease Progression; DNA Fragmentation; Hypertrophy; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mandibular Condyle; Necrosis; Ovalbumin; Rabbits; Temporomandibular Joint Disorders; Time Factors; Tumor Necrosis Factor-alpha

We examined the reversibility of several changes in the lungs and airways of mice immediately after exposure to ovalbumin aerosol and after a period of recovery breathing clean air.. Mice were exposed for 1, 2, 4, 6, 8, or 10 weeks, with recovery in clean air for 1-3 weeks.. Airway collagen content, exhaled NO, airway mucous cell hyperplasia, and lung lavage inflammatory cell content increased upon exposure to ovalbumin aerosol. All parameters except airway fibrosis decreased partially or completely to control values with recovery in clean air.. Airway mucous cell hypertrophy and hyperplasia appear to be completely reversible after recovery in clean air, while exhaled NO and airway inflammation appear to be mostly reversible, except for persistence of lymphocytes in the lung lavage fluid. Airway fibrosis appears to be reversible when mice are exposed to ovalbumin aerosol for periods of up to 4 weeks of exposure, but becomes irreversible after 6 or more weeks of exposure.

Topics: Administration, Inhalation; Animals; Bronchial Diseases; Bronchitis; Collagen; Drug Administration Schedule; Exhalation; Female; Fibrosis; Hyperplasia; Hypertrophy; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Ovalbumin; Pneumonia; Pulmonary Fibrosis; Respiratory Mucosa

The purpose of the research was to observe the influence of the bacterial infection and inhalation vapours on the histologic picture of bronchi and lungs in the course on the experimental asthma induced in guinea pigs. The animals were divided into 6 groups. The animals were immunized by ovalbumin. Group I was control and was subjected to inhalations of physiologic salt solutions. Group II was immunized by the soluble of ovalbumin intraperitoneally and was inhaled with the solution of ovalbumin. Group III was subjected only to inhalation of the ovalbumin. Group IV was inhaled with the solution of formalin alternately. Group V experienced only formalin inhalations. Group VI was infected with Pseudomonas aeruginosa strain and inhaled with the solution of ovalbumin. On the histologic examination of the lung tissue the authors found the atrophy of the lymphatic system, the hypertrophy of the mucous membrane and muscular coat of the bronchi, the accumulation of large amount of mucus in their lumen and the exfoliation of the bronchial epithelium.

Topics: Animals; Asthma; Atrophy; Bronchi; Bronchial Spasm; Epithelium; Formaldehyde; Guinea Pigs; Hypertrophy; Lung; Male; Mucous Membrane; Ovalbumin; Pseudomonas Infections

Repeated injections of monoclonal antibody (mAb) culture supernatants into rat footpads increased the weights of the draining lymph nodes. Immunostained freeze sections showed that injection of MRC OX2, a mAb reacting with rat follicular dendritic cells and MRC OX7 (anti-Thy-1.1), led to gross hypertrophy primarily of the follicular areas, whereas MRC OX6 (anti-rat major histocompatibility complex class II molecules) resulted in selective stimulation of the paracortex. These findings indicate that mAb, when conjugated to certain antigens, would modulate the immune response to these antigens. Consequently, the mAb were conjugated with fluorescein isothiocyanate (FITC) and the humoral response against the hapten measured. The primary anti-FITC antibody response was tenfold stronger than after stimulation with FITC conjugated to a conventional carrier such as ovalbumin, and had some characteristics of a secondary response: a fast increase of IgG level to very high titers and a long duration without further amplification at later antigen challenges.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Monoclonal; Antibody Formation; B-Lymphocytes; Female; Fluorescein-5-isothiocyanate; Fluoresceins; Haptens; Hypertrophy; Lymph Nodes; Male; Ovalbumin; Rats; T-Lymphocytes; Thiocyanates

Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Carbon; Chickens; Corynebacterium; Female; Guinea Pigs; Hypertrophy; Immunity, Cellular; Immunoelectrophoresis; Injections, Intravenous; Liver; Male; Mice; Organ Size; Ovalbumin; Phagocytes; Phagocytosis; Propionibacterium; Propionibacterium acnes; Spleen

Topics: Age Factors; Animals; Body Weight; Chickens; Depression, Chemical; DNA; Drug Antagonism; Electrophoresis; Estradiol; Estrogen Antagonists; Female; Glucose; Glycogen; Hyperplasia; Hypertrophy; Lipid Metabolism; Ovalbumin; Oviducts; Progesterone; Proteins; RNA; Time Factors

Topics: Animals; Animals, Newborn; Antigen-Antibody Reactions; Diphtheria Toxoid; Freund's Adjuvant; Hyperplasia; Hypertrophy; Lymph Nodes; Ovalbumin; Rabbits; Silicon Dioxide