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Local glucocorticoid production in the mouse lung is induced by immune cell stimulation

Local glucocorticoid production in the mouse lung is induced by immune cell stimulation

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Prüfsumme: MD5:140a2e3b32e2064dd00f8592d1089d8f

HOSTETTLER, Nina, Pamela BIANCHI, Carine GENNARI-MOSER, Daniela KASSAHN, Kristina SCHOONJANS, Thomas BRUNNER, 2012. Local glucocorticoid production in the mouse lung is induced by immune cell stimulation. In: Allergy. 67(2), pp. 227-234. ISSN 0105-4538. eISSN 1398-9995. Available under: doi: 10.1111/j.1398-9995.2011.02749.x

@article{Hostettler2012-02Local-18107, title={Local glucocorticoid production in the mouse lung is induced by immune cell stimulation}, year={2012}, doi={10.1111/j.1398-9995.2011.02749.x}, number={2}, volume={67}, issn={0105-4538}, journal={Allergy}, pages={227--234}, author={Hostettler, Nina and Bianchi, Pamela and Gennari-Moser, Carine and Kassahn, Daniela and Schoonjans, Kristina and Brunner, Thomas} }

Hostettler, Nina 2012-02 Bianchi, Pamela Schoonjans, Kristina Background:  Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive steroid hormones, mainly produced by the adrenal glands. However, increasing evidence supports the idea of additional extra-adrenal sources of bioactive GC. The lung epithelium is constantly exposed to a plethora of antigenic stimuli, and local GC synthesis could contribute to limit uncontrolled immune reactions and tissue damage.<br />Methods:  Expression of steroidogenic enzymes and GC synthesis in ex vivo organ cultures was studied in mouse lung tissue after in vivo stimulation of immune cells.<br />Results:  Mouse lung tissue was found to express steroidogenic enzymes required for the synthesis of corticosterone from cholesterol and to synthesize corticosterone in large quantities after immune cell activation by anti-CD3 antibody, lipopolysaccharide, or TNFα. In marked contrast, ovalbumin-induced allergic airway inflammation failed to promote lung GC synthesis. Although the lung expresses all steroidogenic enzymes necessary for de novo synthesis of corticosterone from cholesterol, functional data indicated that inactive serum-derived dehydrocorticosterone is converted to active corticosterone by 11β-hydroxysteroid dehydrogenase 1.<br />Conclusion:  Our results support the notion that local GC synthesis represents a novel immunoregulatory mechanism to limit uncontrolled immune responses in the lung and indicate that defective local steroidogenesis may contribute to the pathogenesis of allergic airway inflammation. Bianchi, Pamela Gennari-Moser, Carine eng Schoonjans, Kristina 2012-02-14T13:27:25Z Kassahn, Daniela 2012-02-14T13:27:25Z Brunner, Thomas Brunner, Thomas deposit-license Kassahn, Daniela Gennari-Moser, Carine First publ. in: Allergy : European Journal of Allergy and Clinical Immunology ; 67 (2012), 2. - pp. 227-234 Hostettler, Nina Local glucocorticoid production in the mouse lung is induced by immune cell stimulation

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