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Yang Liu, Wendy R Kam, Juan Ding, David A Sullivan; The effect of macrolide and tetracycline antibiotics on lipid expression in human meibomian gland epithelial cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3056.
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We recently discovered that azithromycin (AZM), a macrolide antibiotic, can act directly on human meibomian gland epithelial cells (HMGEC) to stimulate their differentiation, enhance their lipid production and promote their holocrine secretion. Because AZM is a cationic amphiphilic drug, we hypothesize that AZM’s mechanism of action involves an increase in cholesterol and phospholipid levels, the formation of lamellar bodies, and the accumulation of lipids in these lamellar lysosomes of HMGEC. The purpose of this investigation was to test this hypothesis. For comparison, we also examined whether other antibiotics, commonly used to treat meibomian gland dysfunction (MGD), can duplicate AZM’s action on HMGEC.
Immortalized HMGEC were cultured in the presence of vehicle, AZM, doxycycline, minocycline or tetracycline (10 µg/ml) for 5 days. Cells were evaluated for cholesterol (Filipin) and neutral lipid (LipidTox) staining, as well as the appearance of lysosomes (LysoTracker) and lamellar bodies (transmission electron microscopy). The lipid composition of cellular lysates was analyzed by high performance thin-layer chromatography.
Our findings demonstrate that AZM stimulates the accumulation of free cholesterol, neutral lipids and lysosomes in HMGEC. This AZM-induced increase of neutral lipid content occurred predominantly within lysosomes and many of these vesicles appeared to be lamellar bodies. Our findings also show that AZM promotes an accumulation of free and esterified cholesterol, as well as phospholipids in HMGEC. In contrast, although tetracycline and its derivatives seemed to increase cholesterol ester and triglyceride levels, they did not duplicate the other AZM effects in HMGEC.
Our results support our hypothesis that AZM induces an increase in cholesterol and phospholipid content, the formation of lamellar bodies, and the accumulation of lipids in these lamellar lysosomes of HMGEC. Our findings also show that these AZM effects are unique, as compared to those of other antibiotics.
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