title: Can tetracycline antibiotics duplicate the ability of azithromycin to stimulate human meibomian gland epithelial cell differentiation?
abstract: OBJECTIVE
  Azithromycin and tetracyclines are commonly prescribed in the United States for the treatment of meibomian gland dysfunction (MGD). The efficacy of these antibiotics has been believed to be their antiinflammatory and antibacterial actions, which suppress MGD-associated posterior blepharitis and growth of lid bacteria. However, we recently discovered that azithromycin can act directly on human meibomian gland epithelial cells (HMGECs) to stimulate their function. In this study, we sought to determine whether tetracycline antibiotics can duplicate this azithromycin effect.
  
  
  METHODS
  Immortalized HMGEC were cultured in the presence of a vehicle, azithromycin, doxycycline, minocycline, or tetracycline for 5 days. Cells were evaluated for cholesterol and neutral lipid staining, and the lipid composition of cellular lysates was analyzed by high-performance thin-layer chromatography.
  
  
  RESULTS
  Our results demonstrate that azithromycin's ability to stimulate the differentiation of human meibomian gland cells is unique, and is not duplicated by doxycycline, minocycline, or tetracycline. Azithromycin, but not the other antibiotics, significantly increased the cellular accumulation of cholesterol, cholesterol esters, phospholipids, and lysosomes. These differentiative actions of azithromycin were paralleled by an increased expression of sterol regulatory element-binding protein 1.
  
  
  CONCLUSIONS
  Our findings show that the stimulatory effects of azithromycin on HMGEC function are unique and are not duplicated by the antibiotics doxycycline, minocycline, or tetracycline. Our results further suggest that this stimulatory influence of azithromycin may contribute to its beneficial effect in treating MGD and its associated evaporative dry eye disease.
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston, MA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kam
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.forename: David A
authors.initials: DA
authors.lastname: Sullivan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015352:Dry Eye Syndromes / Q000188:drug therapy / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008247:Lysosomes / Q000378:metabolism; D008537:Meibomian Glands / Q000166:cytology*; D013754:Tetracyclines / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013754:Tetracyclines; D017963:Azithromycin