PT  - JOURNAL ARTICLE
AU  - Eva Verjans
AU  - Kathleen Reiss
AU  - Norbert Wagner
AU  - Stefan Uhlig
AU  - Klaus Tenbrock
AU  - Christian Martin
TI  - Function of cAMP response element modulator in a murine asthma model
DP  - 2011 Sep 01
TA  - European Respiratory Journal
PG  - p956
VI  - 38
IP  - Suppl 55
4099  - http://erj.ersjournals.com/content/38/Suppl_55/p956.short
4100  - http://erj.ersjournals.com/content/38/Suppl_55/p956.full
SO  - Eur Respir J2011 Sep 01; 38
AB  - Introduction: Several isoforms of the cAMP response element modulator (CREM) act as transcriptional repressors or activators binding to the cAMP response element of different promoters. In contact dermatitis we previously demonstrated the importance of CREM for antigen presenting cell-dependent and independent T cell function and termination of T cellular immune response. In this study we investigated the role of CREM in murine ovalbumin (OVA)-induced airway inflammation.Method: Male wild type (WT) and CREM-knockout animals (CREM-KO) were sensitized i.p. with 10μg OVA in aluminum hydroxide solution (day 0, 14 and 21) and with aerosol (1% OVA on day 28 and 29). On day 35 bronchial responses to nebulized acetylcholine (0.001-1mg) were examined using the flexiVent system (SCIREQ, Montreal, Canada). Inflammatory responses were evaluated by cell counts, cytokine- and IgE measurements in bronchoalveloar lavage (BAL) and serum. Changes in lung tissue were investigated by histology and calculation of the wet/dry-ratio.Results: CREM-KO mice showed an increase in airway responsiveness by elevation in central airway (177%) and tissue resistance (214%) compared to WT (100%). In addition, higher numbers of eosinophils and lymphocytes as well as upregulated Th2 cytokines were found in the BAL of CREM-KO mice. Lung histology indicated increased pulmonary cell infiltration, stronger mucus production and goblet cell hyperplasia.Conclusion: CREM deficiency drives Th2 immune response and influences airway tone as well as mucus production. Our findings suggest that the presence of CREM at least partially protects from the development of asthmatic disease by immunological and non-immunological mechanisms.