Abstract
Budesonide (Bud), one of the most widely used lung medicines, is currently used as a repurposing medicine for immunoglobulin A nephropathy (IgAN) treatment. The progression of IgAN is related to inflammation involving macrophages and podocytes. The present study aimed to explore the effects of Bud on classically activated (M1)/alternatively activated (M2) macrophage polarization and podocyte injury under lipopolysaccharide (LPS)-induced inflammatory stress in vitro. Anti-inflammatory bioinformation of Bud was identified based on the Gene Expression Omnibus database. RAW264.7 cells were treated with normal medium, LPS, curcumin (Cur, positive control), or Bud 5, 10, or 20 µM. The expression levels of inducible nitric oxide synthase (iNOS), TNF-α, mannose receptor (CD206) and arginase (Arg)-1 were quantified by western blotting. The collected supernatants from macrophages were termed (Nor)MS, (LPS)MS, (Cur)MS and (Bud)MS. The TNF-α, IL-1β and nitric oxide (NO) levels in the supernatants were evaluated by ELISA and Griess assay. The podocytes were cultured in different supernatants and their survival rates were assessed by bromodeoxyuridine assay. TNF signaling is an important pathway by which Bud exerts anti-inflammatory activities. Compared with the LPS group, 5, 10 and 20 µM Bud significantly increased Arg-1 and decreased iNOS expression (Six: P<0.05) and 20 µM Bud significantly increased Arg-1 and CD206 and decreased iNOS and TNF-α expression (Four: P<0.05). Cur significantly decreased iNOS and TNF-α expression (Two: P<0.05). Compared with LPS, 5, 10 and 20 µM Bud and Cur significantly decreased TNF-α, IL-1β and NO levels (All: P<0.05). The podocyte survival rates of (Bud)MS and (Cur)MS were significantly higher than those of (LPS)MS (Four: P<0.05). The protective effect of Bud on podocyte injury is related to its modulation of M1/M2 polarization.