title: Cell-type specific regulation of galectin-3 expression by glucocorticoids in lung Clara cells and macrophages.
abstract: Bronchiolar Clara cells are integral components of lung homeostasis, predominantly distributed in distal airways. In addition to the 16 kDa Clara cell protein, a major secretory product with anti-inflammatory effects, rat Clara cells express the glycan-binding protein galectin-3 and secrete it into the airways. Given the essential role of galectin-3 in the control of inflammation and the well-established function of glucocorticoids (GCs) in lung physiology, here we investigated whether galectin-3 is a target of the regulatory effects of GCs. Adult male rats were subjected to bilateral adrenalectomy and the lungs were processed for light and transmission electron microscopy, immunoelectron microscopy and Western blot analysis. Profound changes in bronchiolar Clara cells and macrophage morphology could be observed by electron microscopy after adrenalectomy. While specific galectin-3 staining was detected in the nucleus and cytoplasm of Clara cells and macrophages from control animals, cytoplasmic galectin-3 expression was dramatically reduced after adrenalectomy in both cell types. This effect was cell-specific as it did not affect expression of this lectin in ciliated cells. After dexamethasone treatment, galectin-3 expression increased significantly in the nucleus and cytoplasm of macrophages and Clara cells. Western blot analysis showed a clear decrease in galectin-3 expression in ADX animals, which was recovered after a 7-day treatment with dexamethasone. In peritoneal macrophages, galectin-3 expression was also dependent on the effects of GCs both in vivo and in vitro. Our results identify a cell type-specific control of galectin-3 synthesis by GCs in lung bronchiolar Clara cells and interstitial macrophages, which may provide an alternative mechanism by which GCs contribute to modulate the inflammatory response.
authors.affiliation: Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Cristina A
authors.initials: CA
authors.lastname: Maldonado
authors.forename: Victoria
authors.initials: V
authors.lastname: Sundblad
authors.forename: Mariana
authors.initials: M
authors.lastname: Salatino
authors.forename: Jorge
authors.initials: J
authors.lastname: Elia
authors.forename: Luciana N
authors.initials: LN
authors.lastname: García
authors.forename: Carolina
authors.initials: C
authors.lastname: Leimgruber
authors.forename: Diego O
authors.initials: DO
authors.lastname: Croci
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055745:Bronchioles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D037502:Galectin 3 / Q000096:biosynthesis*; D015870:Gene Expression; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D051381:Rats; D017208:Rats, Wistar
chemical_list: D037502:Galectin 3; D005938:Glucocorticoids; D003907:Dexamethasone