title: Fluticasone induces apoptosis in peripheral T-lymphocytes: a comparison between asthmatic and normal subjects.
abstract: Apoptosis is an important mechanism allowing inflammation to be limited. Glucocorticoids are the most effective anti-inflammatory agents in asthma therapy and induce cell apoptosis. Since T-lymphocytes are critically involved in airway inflammation in asthma, the effects of fluticasone propionate (FP) on apoptosis in unstimulated and in interleukin (IL)-2 stimulated peripheral blood T-lymphocytes (PBTs) isolated from 14 normal and 19 mild-to-moderate asthmatic subjects were evaluated. Apoptosis was evaluated by: deoxyribonucleic acid (DNA) fragmentation electrophoresis, DNA content, annexin V binding, apoptosis related markers (Fas, B-cell lymphona leukaemia-2 (Bcl-2), Bax, and CD25), and by electron microscopy. FP induced apoptosis in unstimulated PBTs of normal and asthmatic subjects in a time-dependent fashion. In asthma, this effect was associated with a significant decrease of Bcl-2 expression, and with an increase of Bax/Bcl-2 ratio. In PBTs of asthmatics, FP also reduced Fas and CD25 expression. Moreover, in IL-2-stimulated PBTs from both asthmatics and normal subjects, FP was able to induce apoptosis and to reduce Bcl-2, Fas and CD25 expression, whereas negligible effects were detected on Bax expression. This study shows that the glucocorticosteroid, fluticasone, increases apoptosis and modulates expression of apoptosis-related markers in unstimulated and in interleukin-2 stimulated T-lymphocytes. This points towards a potential mechanism by which fluticasone exerts its anti-inflammatory effects.
authors.affiliation: Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Melis
authors.forename: L
authors.initials: L
authors.lastname: Siena
authors.forename: E
authors.initials: E
authors.lastname: Pace
authors.forename: M
authors.initials: M
authors.lastname: Gjomarkaj
authors.forename: M
authors.initials: M
authors.lastname: Profita
authors.forename: A
authors.initials: A
authors.lastname: Pirazzoli
authors.forename: M
authors.initials: M
authors.lastname: Todaro
authors.forename: G
authors.initials: G
authors.lastname: Stassi
authors.forename: G
authors.initials: G
authors.lastname: Bonsignore
authors.forename: A M
authors.initials: AM
authors.lastname: Vignola
mesh_terms: D000328:Adult; D000730:Androstadienes / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D000068298:Fluticasone; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000032:analysis
chemical_list: D000730:Androstadienes; D017304:Annexin A5; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; C494826:BAX protein, human; D005938:Glucocorticoids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D004247:DNA; D000068298:Fluticasone