Dioscin ameliorates silica-aggravated systemic lupus erythematosus via suppressing apoptosis and improving LC3-associated phagocytosis in MRL/lpr mice.

Inhalation of silica not only directly leads to silicosis locally, but also results in various types of autoimmune diseases systemically, most commonly systemic lupus erythematosus (SLE). Little is known about the etiopathogenesis of silica-aggravated SLE to date, however, abnormal apoptosis and impaired apoptotic clearance have been reported to be closely related to the occurrence of SLE. LC3-associated phagocytosis (LAP) is a non-canonical form of autophagy, which plays a crucial role in mediating the clearance of apoptotic cells. Here we showed that the excessive accumulation of apoptotic debris in MRL/lpr mice exposed to silica might be due to the increased cell apoptosis and defective LAP caused by silica, thus accelerating the occurrence and progression of silica-aggravated SLE. Dioscin is an active ingredient in the family of Dioscoreaceae and is reported to possess multiple pharmacological activities, including anti-inflammatory, anti-apoptotic and autophagy-promoting properties. However, its role in SLE aggravated by silica exposure has not been investigated. In our study, we confirmed that dioscin decreased the accumulation of apoptotic debris by suppressing the excessive cell apoptosis and improving the LAP of immune cells in lung and spleen, leading to subsequent dramatically ameliorated lupus-like symptoms in silica-exposed MRL/lpr mice.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.