Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Airway hyperresponsiveness, airway eosinophilia and increased IgE levels in serum are the important characteristic features of asthma. We evaluated the potential of para-Bromophenacyl bromide (PBPB), a known phospholipase A(2) inhibitor, on allergen-induced airway hyperresponsiveness in a mouse model. We sensitized and challenged mice with ovalbumin (OVA) to develop airway hyperresponsiveness as assessed by airway constriction and airway hyperreactivity (AHR) to methacholine (MCh) induced by allergen. The mice were orally treated with PBPB (0.1, 1 and 10 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect on airway constriction and AHR to MCh. Determination of OVA-induced airway constriction and AHR to MCh were performed by measuring specific airway conductance (SGaw) using non-invasive dual-chamber whole body-plethysmography. We observed that PBPB (1 mg/kg) significantly reduced OVA-induced airway constriction and AHR to MCh (p<0.01). PBPB (1 mg/kg) treatment significantly inhibited PLA(2) activity in the BAL fluid. Cytokine analysis of the BAL fluid revealed that PBPB caused an increase in interferon-gamma (IFN-gamma) (p<0.02) and a decrease in interleukin-4 (IL-4) (p<0.05) and interleukin-5 (IL-5) (p<0.05) levels. The OVA-specific serum IgE levels (p<0.01) and the BAL eosinophils (p<0.001) were also reduced significantly. Thus, PBPB is capable of modulating allergen induced cytokine levels and serum IgE levels, and alleviating allergen induced airway hyperresponsiveness and eosinophils in mice. These data suggest that PBPB could be useful in the development of novel agents for the treatment of allergen induced airway hyperresponsiveness.
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PMID:Para-Bromophenacyl bromide alleviates airway hyperresponsiveness and modulates cytokines, IgE and eosinophil levels in ovalbumin-sensitized and -challenged mice. 1545 21

We previously reported that 4-hydroxy-3-methoxybenzaldehyde has the most potent anti-inflammatory and analgesic activity of eight phenolic compounds obtained from the dried roots of Gastrodiaelata (GE) Blume (Orchidaceae); its activity may be related to inhibition of cyclooxygenase activities and oxidation. In the present study, the effects of nine phenolic compounds from GE on immediate-phase (IAR) and late-phase (LAR) asthmatic responses after aerosolized-ovalbumin (OA) challenge were evaluated by determining the specific airway resistance (sRaw) using a double-chambered plethysmograph in conscious guinea pigs with IgE-mediated asthma. Furthermore, recruitment of leukocytes, histamine release, and eosinophil peroxidase (EPO) and phospholipase A(2) (PLA(2)) activities were determined in bronchoalveolar lavage fluids (BALF) 24h after the antigen challenge. 4-Hydroxy-3-methoxybenzyl alcohol (12.5mg/kg) significantly (p<0.05) inhibited sRaw in IAR and in LAR by 51.97+/-4.96% and 39.93+/-3.46%, respectively, compared to that of the controls. Further, hydroxy-3-methoxybenzyl alcohol significantly (p<0.05) inhibited recruitment of leukocytes in accordance with amelioration of eosinophilia and neutrophilia, histamine (30.66+/-5.20%), EPO activity (21.58+/-2.02%), and specific PLA(2) activity (16.60+/-2.52%) in BALF compared with the control. In addition, bis-(4-hydroxyphenyl) methane, 4-hydroxy-3-methoxybenzoic acid, and 4-hydroxy-3-methoxybenzaldehyde (12.5mg/kg) significantly (p<0.05) inhibited sRaw, while bis-(4-hydroxyphenyl) methane, benzyl alcohol, and 4-hydroxybenzaldehyde at 12.5mg/kg significantly (p<0.05) inhibited leukocytes, histamine, EPO and PLA(2) activities in BALF compared with the controls. The phenolic glycoside, parishin had less activity compared to aglycones, 4-hydroxybenzyl compounds. These results suggest that the C(4) hydroxy and C(3) methoxy radicals in benzyl alcohols and aldehydes play important roles in mediating the anti-asthmatic activities of these compounds.
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PMID:Anti-asthmatic activity of phenolic compounds from the roots of Gastrodia elata Bl. 1987 15

It is well known that the prevalence of asthma is higher in athletes, including Olympic athletes, than in the general population. In this study, we analyzed the mechanism of exercise-induced bronchoconstriction by using animal models of athlete asthma. Mice were made to exercise on a treadmill for a total duration of 1 week, 3 weeks, or 5 weeks. We analyzed airway responsiveness, BAL fluid, lung homogenates, and tissue histology for each period. In mice that were treated (i.e., the treatment model), treatments were administered from the fourth to the fifth week. We also collected induced sputum from human athletes with asthma and analyzed the supernatants. Airway responsiveness to methacholine was enhanced with repeated exercise stimulation, although the cell composition in BAL fluid did not change. Exercise induced hypertrophy of airway smooth muscle and subepithelial collagen deposition. Cysteinyl-leukotriene (Cys-LT) levels were significantly increased with exercise duration. Montelukast treatment significantly reduced airway hyperresponsiveness (AHR) and airway remodeling. Expression of PLA2G4 (phospholipase A2 group IV) and leukotriene C4 synthase in the airway epithelium was upregulated in the exercise model, and inhibition of PLA2 ameliorated AHR and airway remodeling, with associated lower levels of Cys-LTs. The levels of Cys-LTs in sputum from athletes did not differ between those with and without sputum eosinophilia. These data suggest that AHR and airway remodeling were caused by repeated and strenuous exercise. Cys-LTs from the airway epithelium, but not inflammatory cells, may play an important role in this mouse model.
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PMID:Cysteinyl Leukotriene Synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling. 3248 47