Wyniki wyszukiwania - Biblioteka Nauki

1

The role of leukotrienes in the pathophysiology of bronchial asthma - the perspective of therapy

100%

Wojnowski P. , Patkowski J.

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tom 51

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nr 5

499-514

EN

Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid, are pro-inflammatory mediators with various biological activities, including mechanisms relevant to the pathogenesis of bronchoobturation in bronchial asthma. This article reviews the evidence on their role in the pathophysiology of asthma as well as on the efficacy of recently developed antileukotriene agents. Leukotriene receptor antagonists and synthesis of inhibitors show promise as a new pharmacologic approach to the treatment of this disease.

2

Cytokines in allergic inflammatory process

100%

Rutkowski R. , Moniuszko M. T. , Moniuszko T.

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tom 55

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nr 4

587-603

EN

In our review article we intend to show the importance of IL-4, IL-5, IL-13, IL-10, IFN gamma and IL-12 in pathomechanism of allergic inflammatory process, expecially in bronchial asthma. We also want to ilustrate the relationships between lymphocytes T, monocytes, macrophages, eosinophils and other inflammatory cells which take part in allergic inflammation.

3

Bronchial asthma as a multifactorial disease

80%

Jasek M.

Postępy Higieny i Medycyny Doświadczalnej

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2003

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tom 57

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nr 3

263-273

EN

Asthma is a common condition that results from the interaction of an unknown number of genes with envitonmental factors. Here, we describe the recent advances in this field including results of genome-wide searches for susceptibility genes.

4

The role of PTEN in allergic inflammation

80%

Lee Y. C.

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2004

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tom 52

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nr 4

250-254

EN

Bronchial asthma is a chronic inflammatory disease of the airways, characterized by airway eosinophilia, goblet cell hyperplasia with mucus hyper-secretion, and hyper-responsiveness to inhaled allergens and to non-specific stimuli. Eosinophil accumulation and subsequent activation in bronchial tissues play critical roles in the pathophysiology of bronchial asthma. Many inflammatory mediators attract and activate eosinophils via signal transduction pathways involving an enzyme phosphatidylinositol 3-kinase (PI3- kinase). Studies using wortmannin, a specific inhibitor of PI3-kinase, have revealed the involvement of PI3-kinase in the biochemical transduction of activation signals generated by many inflammatory mediators in eosinophils. Wortmannin prevents the development of airway inflammation, either by inhibiting the eosinophil infiltration of bronchial tissues or their activation on arrival. Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN opposes the action of PI3-kinase by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. Recently we have demonstrated that PTEN expression is diminished in airway epithelial cells of antigen-sensitized and -challenged mice. Administration of PI3-kinase inhibitors or adenoviruses carrying PTEN complementary DNA remarkably reduces eosinophil levels and inflammation. One likely mechanism for this reduction is PTEN-mediated eosinophil degranulation and suppression of interleukin (IL)-4 and IL-5. These findings indicate that use of PTEN may be a good therapeutic strategy for the management of allergic inflammation.

5

Effect of short-term and chronic glucocorticoid therapy on lymphocyte glucocorticoid receptor number in patients with asthma

80%

Grzanka A. , Rogala B.

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nr 5

327-334

EN

Glucocorticoid (GCs) hormones are widely used in the treatment of bronchial asthma. However, not all aspects of their pharmacological effects are well understood as yet. It is know that the effects of GCs are mediated through GC receptors (GCRs). We sought to evaluate the effect of short-term and chronic GC therapy on GCR number in peripheral blood lymphocytes, the relationship between GCR number and cortisol concentrations in asthma patients treated with GCs as well as the response to GC therapy in various pictures of this disease. Sixty-nine patients with bronchial asthma were investigated. Thirty-five of them had received steroid therapy: 18 patients for 1 to 15 years and 17 patients for 13 days after a prior 3 month discontinuation of steroid treatment. The control group consisted of 28 healthy, age matched volunteers. GCR numbers were determined using tritriated dexamethasone as a ligand. The scatchard method was applied to calculate the maximal specific binding and the dissociation constant. The number of receptor sites per lymphocyte was calculated. Cortisol was measured by radioimmunoassay. Lymphocyte GCR numbers in patients with bronchial asthma who were not treated with steroids, did not differ from age-matched healthy persons (means 8115+- 812 and 7905+- 832). A significant decrease in receptor number was seen in patients receiving steroid therapy. There was also a significant difference in receptor number between the groups with short-course (mean 3741+- 549) and chronic steroid therapy (mean 4885+- 1095). The number of GCRs did not correlate with age, sex, clinical state or serum cortisol concentration in either group.

6

Recent advances in understanding how interleukin 13 signals are involved in the pathogenesis of bronchial asthma

70%

Izuhara K. , Umeshita R. , AkaiwaM. , Shirakawa T. , Deichmann K. A. , Arima K. , Yu B. , Hamasaki N. , Hopkin J. M.

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nr 5

505-512

EN

The prevalence of allergic disease has dramatically increased in recent decades, especially in urban and industralized areas. Allergic disease are disorders of the immune system, the results of complex interactions among various genetic and environmetal factors. Among them, the important role of interleukin 13 (IL-13), a TH2-type cytokine, has recently emerged in the pathogenesis of bronchial asthma. Based on studies using mice, great attention has been paid to the direct effects of IL-13 on bronchial tissues. In this review, we describe recent advances in understanding the signal transduction mechanism of IL-13, the infolvement of IL-13 signal-related genes as genetic factors in the pathogenesis of bronchial asthma, and the expression of IL-13 receptor on bronchial tissues. We describe potential strategies for targeting IL-13 signals to improve allergic states.

7

CD80 and CD86 expression on LPS-stimulated monocytes and effect of CD80 and CD86 blockade on IL-4 and IFN-gamma production in nonatopic bronchial asthma

70%

Rutkowski R. , Moniuszko T. , Stasiak-Barmuta A. , Kosztyla-Hojna B. , Alifier M. , Rutkowski K. , Tatarczuk-Krawiel A.

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tom 51

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nr 6

421-428

EN

CD80 and CD86 seem to play an important role in the allergen induced secretion of IL-5 and IL-13. Up till now, the expression of CD80 (B7.1) and CD86 (B7.2) on monocytes and kinetics of these molecules expression on lipopolysaccharide?stimulated monocytes in nonatopic asthma have not been defined. Using monoclonal antibodies we have compared the expression of CD80 (B7.1) and CD86 (B7.2) on monocytes of healthy persons and nonatopic asthmatic patients. We have also assessed the effect of CD80 and CD86 inactivation on interleukin (IL)-4 and interferon gamma (IFN-gamma production in nonatopic asthmatics and healthy subjects. We found that low expression of CD80 on studied monocytes (1.64+0.65 vs. 3.53+1.43%) and moderate expression of CD86 (41.25+134 vs. 49.46+11.49%) were characteristic for asthma. In nonatopic asthma patients inactivation of CD80 or CD86 blockade significantly reduced IFN-gamma production by T lymphocytes (p<0.02; p<0.03). In both studied groups anti-CD80 antibodies did not diminish T lymphocytes` production of IL-4. However anti-CD86 antibodies significantly (p<0.04) reduced the IL-4 concentration in culture supernatants. Our results confirm that both CD80 and CD86 molecules play on important role in the maintenance and amplification of inflammatory process. It suggests that in the inflammatory process that occurs in the nonatopic bronchial asthma Th1 as well as Th2 lymphocytes are equally important

8

Comparison of leukocyte populations from bronchoalveolar lavage and induced sputum in evaluation of cell composition and nitric oxide production in patients with bronchial asthma

60%

Bienkowska-Haba M. , Cembrzynska-Nowak M. , Liebhart J. , Dobek R. , Liebhart E. , Siemieniec I. , Panaszek B. , Obojski A. , Malolepszy J.

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tom 50

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nr 1

75-83

EN

Bronchoalveolar lavage (BAL) or induced sputum (IS) techniques may provide leukocytes for the evaluation of airway inflammatory response in bronchial asthma. The aim of the present study was to compare features of leukocyte populations obtained by the two different methods regarding the cell types and their activity in patients with bronchial asthma. The nitric oxide (NO) level released from the cells was measured as a marker of their activity. Pulmonary leukocytes were obtained from the BAL and IS of 11 asthmatic patients in stable condition at the time of the study. The BAL and IS leukocyte populations varied in cell count and NO production. Macrophages were the predominant leukocyte population in BAL (Me = 83.0%, range 67.9-88.4%), whereas sputum sediments were found to consist mainly of neutrophils (Me = 55.7%, range 29.0-64.9%). The IS leukocytes released much more NO (p = 0.0022) than the BAL leukocytes. In spite of these quantitative differences, a similar pattern of NO production was observed in BAL and in IS cells. Both BAL and IS leukocyte populations produced almost the same amounts of NO before and after lipopolysaccharide stimulation (p = 0.9063, p = 0.4801, respectively). Furthermore, a slight positive correlation (RS = 0.5578, p=0.0594) was noticed between the neutrophil percentages and NO levels produced by BAL cells, whereas in IS a statistically significant correlation between the percentage of neutrophils and the levels of NO (RS = 0.6643, p = 0.0184) was observed. In conclusion, the BAL and IS leukocyte populations are different in cell type, their size and activity. Depending on the asthma severity and the type of cells needed in a study, either BAL or IS specimens may be chosen as a source of pulmonary leukocytes. The use of IS as a noninvasive technique is supposed to be potential value particularly in the study of the airway inflammatory response mediated mainly by neutrophils, i.e. during and/or after exacerbation of the disease. Based on our results, a possible contribution of neutrophils in the production of NO in the airways of asthmatic patients can be proposed apart from other cells such as macrophages.