title: Local glucocorticoid production in the mouse lung is induced by immune cell stimulation.
abstract: 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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Experimental Pathology, Institute of Pathology, University of Bern, Switzerland.
authors: N
authors: N
authors: Hostettler
authors: P
authors: P
authors: Bianchi
authors: C
authors: C
authors: Gennari-Moser
authors: D
authors: D
authors: Kassahn
authors: K
authors: K
authors: Schoonjans
authors: N
authors: N
authors: Corazza
authors: T
authors: T
authors: Brunner
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000096:biosynthesis*; D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D013250:Steroid Hydroxylases