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Effect of phosphodiesterase 4 (PDE4) inhibitors on eotaxin expression in human bronchial epithelial cells

100%

Paplinska M. , Chazan R. , Grubek-Jaworska H.

nr 3

The increasing number of eosinophils into bronchoaelvolar space is observed during noninfectious inflammatory lung diseases. Eotaxins (eotaxin-1/CCL11, eotaxin-2/CCL24, eotaxin-3/CCL26) are the strongest chemotactic agents for eosinophils. Inhibitors of phosphodiesterase 4 (PDE4), the enzyme decomposing cAMP, are anti-inflammatory agents which act through cAMP elevation and inhibit numerous steps of allergic inflammation. The effect of PDE4 inhibitors on eotaxin expression is not known in details. The aim of our study was to evaluate the influence of PDE4 inhibitors: rolipram and RO-20-1724 on expression of eotaxins in bronchial epithelial cell line BEAS-2B. Cells were preincubated with PDE4 inhibitors or dexamethasone for 1 hour and then stimulated with IL-4 or IL-13 alone or in combination with TNF-. After 48 hours eotaxin protein level was measured by ELISA and mRNA level by real time PCR. Results: PDE4 inhibitors decreased CCL11 and CCL26 expression only in cultures co-stimulated with TNF-. In cultures stimulated with IL-4 and TNF- rolipram and RO-20-1724 diminished CCL11 mRNA expression by 34 and 37%, respectively, and CCL26 by 43 and 47%. In cultures stimulated with IL-13 and TNF- rolipram and RO-20-1724 decreased expression of both eotaxins by about 50%. These results were confirmed at the protein level. The effect of PDE4 inhibitors on eotaxin expression in BEAS-2B cells, in our experimental conditions, depends on TNF- contribution.

Computerized "mycobacterium" type recognition using numerical data base of mycolic acids elution profiles

100%

Glapiński J. , Walkiewicz R. , Safianowska A. , Grubek-Jaworska H.

tom Vol. 24, no. 1

25-38

The aim of this study was to create a standarized numerical data base of high pressure liquid chromatography elution (HPLC) profiles of mycolic acids extracted from the "Mycobacterium" cell wall, with 28 mycobacterial American Type Culture Collection (ATCC) strains taken as a reference for the study. The final result of our work is a notebook of standarized elution profiles and a computer program (MYCAM) for highly effective and specific automatic "Mycobacterium" species identification.

Effects of the phosphodiesterase-4 inhibitor rolipram on lung resistance and inflammatory reaction in experimental asthma

88%

Nejman-Gryz P. , Grubek-Jaworska H. , Glapinski J. , Hoser G. , Chazan R.

nr 4

229-239

The aim of this study was to evaluate the influence of pretreatment with the phosphodiesterase-4 inhibitor rolipram on pulmonary resistance, influx of inflammatory cells, and histamine concentration in bronchoalveolar lavage fluid (BALF) during an experimental asthmatic reaction induced in ovalbumin (OA)-sensitized guinea pigs, challenged with OA inhalation. The experiment was performed in three groups of guinea pigs: two experimental groups, pretreated with rolipram or dexamethasone, and a control group without any pretreatment. Lung resistance (LR) was continuously recorded under suppression of spontaneous breathing during early asthmatic reaction. BALF was obtained before and at three time points up to 24 hr after the challenge. In the untreated, control animals a transient, significant increase in neutrophils, total and CD4+ lymphocytes, macrophages, eosinophils, and in histamine concentration in BALF was noted. Pretreatment with rolipram significantly reduced LR, eosinophils infiltration, and histamine release into the bronchoalveolar space during the early asthmatic reaction. These effects were generally comparable with those of dexamethasone, except that dexamethasone also reduced the influx of neutrophils into BALF.