Budesonide effects on Clara cell under normal and allergic inflammatory condition.
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.
Roth
Felix Daniel
FD
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,
Quintar
Amado Alfredo
AA
Uribe Echevarría
Elisa M
EM
Torres
Alicia Inés
AI
Aoki
Agustín
A
Maldonado
Cristina Alicia
CA
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
D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D005938:Glucocorticoids; C556390:Scgb1a1 protein, mouse; D019819:Budesonide; D014598:Uteroglobin; D019392:Cytochrome P-450 CYP2E1