Protective effects of budesonide on LPS‑induced podocyte injury by modulating macrophage M1/M2 polarization: Evidence from in vitro and in silico studies

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.

Lactobacillus plantarum 45 activates SHP2 through inhibition of oxidative stress to regulate osteoblast and osteoclast differentiation

“…It has been found that activated macrophages are closely linked to the severity of osteoporosis [ 25 ]. Secretion factors are determinants for regulation of macrophages on bone cells, and specific cytokines are released in response to stimulating factors such as LPS, causing cellular damage and oxidative stress [ 26 ]. Macrophages have immunomodulatory effects on in vitro tissue recovery and osteoblast differentiation under stimulation by benign factors [ 27 ], such as the fact that M2 macrophage-secreted OPG stimulates the differentiation and activation of osteoblast precursor cells [ 28 ] (e.g., mesenchymal stem cells, MSCs), increases bone mineralization, and promotes bone homeostasis and bone cell regeneration [ 29 ].…”

Desmosterol-driven atypical macrophage polarization regulates podocyte dynamics in diabetic nephropathy

“…On the other hand, the podocytes may also regulate macrophage polarization through various signaling mechanisms. They secrete cytokines and chemokines, such as IL-6 and Chemokine (C-C motif) ligand 2 (CCL2), which can recruit macrophages and often promote a pro-inflammatory M1 phenotype, particularly in disease states like DN [ 28 ]. Additionally, podocytes produce growth factors like TGFβ1, known to drive macrophages towards an M2, tissue-repairing phenotype.…”