Treatment of experimental asthma by decoy-mediated local inhibition of activator protein-1

in American Journal of Respiratory & Critical Care Medicine (2005), 172(6), 671-678

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL ... [more ▼]

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes contain binding sites for activator protein-1 (AP-1) within their promoter and are therefore believed to depend on AP-1 for their expression, suggesting that this transcription factor could be of particular importance in asthma pathophysiology. Objective: To clarify the role of AP-1 in the effector phase of pulmonary allergy. Methods: Ovalbumin (OVA)-sensitized mice were intratracheally given decoy oligodeoxyribonucleotides (ODNs) specifically directed to AP-1 or scrambled control ODNs before challenge with aerosolized OVA. Twenty-four hours after the last OVA challenge, airway hyperresponsiveness was measured and allergic airway inflammation was evaluated quantitatively. AP-1 decoys were localized using flow cytometry and immunohistochemistry. AP-1 activity in the lung was assessed using electrophoretic mobility shift assay. Measurements and Main Results: Intratracheally delivered AP-1 decoys efficiently targeted airway immune cells, thus precluding AP-1 activation on OVA challenge. Decoy-mediated local inhibition of AP-1 resulted in significant attenuation of all the pathophysiologic features of experimental asthma-namely, eosinophilic airway inflammation, airway hyperresponsiveness, mucous cell hyperplasia, production of allergen-specific immunoglobulins, and synthesis of IL-4, IL-5, and IL-13. Scrambled control ODNs had no detectable effects. Conclusions: Our results reveal a key role for AP-1 in the effector phase of pulmonary allergy and indicate that specific AP-1 inhibition in the airways may have therapeutic value in the control of established asthma. [less ▲]

Long-term photometry of variables at ESO. III. The third data catalogue (1990-1992).

in Astronomy and Astrophysics. Supplement Series (1995), 109

In this paper we present the third catalogue of photometric data in the Stroemgren system obtained during the period October 1990-January 1992 in the framework of the Long-Term Photometry of Variables ... [more ▼]

In this paper we present the third catalogue of photometric data in the Stroemgren system obtained during the period October 1990-January 1992 in the framework of the Long-Term Photometry of Variables (LTPV) program at the European Southern Observatory. The catalogue is available in computer readable form at the Centre de Donnees de Strasbourg. [less ▲]