Necrox-5 Ameliorates Inflammation By Skewing Macrophages to the M2 Phenotype

Capsular contracture around implants is the most common local complication after silicone breast implants, and there are currently no successful preventive treatments. Mounting evidence suggests that macrophage polarization plays a crucial role in the progression of the fibrotic capsule formation. This study aimed to evaluate the role of NecroX-5, a powerful anti-inflammatory agent, on the functional plasticity of macrophages and the possible underlying mechanism using RAW264.7 cells, a murine macrophage cell line. The change in cell morphology was examined by scanning electron microscopy. The expression of CD206, arginase (Arg)-1, inducible nitric oxide synthase (iNOS), and phosphor-signal transducer and activator of transcription (pSTAT) 6 were examined by western blotting. The production of inflammatory cytokines was detected by enzyme-linked immunosorbent assays, and statistical comparisons were made. The results showed that treatment of RAW264.7 cells with NecroX-5 caused an elongated shape in comparison to non-treated cells. The expression levels of macrophage mannose receptor CD206 and Arg-1, specific markers of M2 cells, were significantly upregulated by NecroX-5 treatment, while those of iNOS (M1 macrophages) was decreased. In addition, NecroX-5 significantly reduced the secretion of inflammatory cytokines, while IL-4 and IL-13 secretion in the supernatant was significantly enhanced. Significantly reduced pSTAT6 expression was also observed in NocroX-5-treated cells. These data suggested that NecroX-5 might dampen the capsular contracture and fibrosis by switching the M1 phenotype to the M2 phenotype due to pSTAT6 induction.

 

Key Words: Capsular contracture; Macrophages; iNOS; Arg-1; NecroX-5