title: Budesonide effects on Clara cell under normal and allergic inflammatory condition.
abstract: Clara cells are nonciliated secretory cells implicated in lung homeostasis by the synthesis of immunomodulatory and host defense products, being one of the most important the CC16 protein. In this study, we compared the effects of budesonide (BUD), an inhaled corticoid, on Clara cell biology and its ability to reverse morphofunctional changes induced in an allergic airway hyper-responsiveness mouse model. In normal mice, exposure to BUD induced morphological changes compatible with a state of maximal differentiation on CC16 positive cells which developed a prominent cupola filled up with numerous mitochondria rich in CYP2E1, a member of the cytochrome P450 family. Consequently, CYP2E1 expression raised significantly. Exposure to OVA provoked hypertrophy of Clara cells and an increment in their number per millimeter of basal membrane. These cells acquired a mucous cell phenotype characterized by a notorious expansion of the secretory granular content. Synthesis of CC16 was greatly up-regulated concurrent to the finding of MUC5AC expression and the increment of epidermal growth factor receptor (EGFR). Mitochondrial content decreased significantly with a consequent reduction in CYP2E1 expression. After BUD treatment of OVA-challenged animals, the majority of Clara cells regained their normal morphology and functional characteristics; CYP2E1 levels raised when compared to the OVA exposed group. The BUD potential to differentiate Clara cells appeared to be important for the regression of the profound changes generated by the allergic injury. These results demonstrated the wide range of stimuli that can modify different aspects of Clara cell biology, and highlighted the effects of budesonide as a modulator of P450 enzymes, which probably contributes to a complementary antiinflamatory activity.
authors.affiliation: Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Pabellón de Biología Celular, Haya de la Torre y Enrique Barros, 5000 Córdoba, Argentina,
authors.forename: Felix Daniel
authors.initials: FD
authors.lastname: Roth
authors.forename: Amado Alfredo
authors.initials: AA
authors.lastname: Quintar
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Uribe Echevarría
authors.forename: Alicia Inés
authors.initials: AI
authors.lastname: Torres
authors.forename: Agustín
authors.initials: A
authors.lastname: Aoki
authors.forename: Cristina Alicia
authors.initials: CA
authors.lastname: Maldonado
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000473:pathology; D001993:Bronchodilator Agents / Q000494:pharmacology; D019819:Budesonide; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006967:Hypersensitivity / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D015854:Up-Regulation / Q000187:drug effects; D014598:Uteroglobin / Q000096:biosynthesis
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; C556390:Scgb1a1 protein, mouse; D019819:Budesonide; D014598:Uteroglobin; D019392:Cytochrome P-450 CYP2E1