Tumor necrosis factor-α-induced protein 8-like-2 is involved in the activation of macrophages by Astragalus polysaccharides in vitro

Mol Med Rep. 2018 May;17(5):7428-7434. doi: 10.3892/mmr.2018.8730. Epub 2018 Mar 13.

Abstract

In previous years, studies have shown that Astragalus polysaccharides (APS) can improve cellular immunity and humoral immune function, which has become a focus of investigations. Tumor necrosis factor‑α‑induced protein 8‑like 2 (TIPE2) is a negative regulator of immune reactions. However, the effect and underlying mechanisms of TIPE2 on the APS‑induced immune response remains to be fully elucidated. The present study aimed to examine the role of TIPE2 and its underlying mechanisms in the APS‑induced immune response. The production of nitric oxide (NO) was detected in macrophages in vitro following APS stimulation. In addition, the present study interfered with the expression of TIPE2 in macrophages, and examined the production of cytokines, NO and components of the mitogen‑activate protein kinase (MAPK) signaling pathway following APS stimulation. The results showed that APS was able to activate macrophages by inducing the production of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑6 and NO. Furthermore, RAW264.7 cells were stimulated with APS when TIPE2 was silenced, and it was found that the production of TNF‑α, IL‑6, IL‑1β and NO were upregulated, and the signaling pathway of MAPK was activated. Taken together, these results demonstrated that TIPE2 had an important negative effect on the APS‑induced production of inflammatory cytokines and NO via the MAPK signaling pathway.

Keywords: Astragalus polysaccharides; macrophages; activation; downregulation; tumor necrosis factor-α-induced protein 8-like-2.

MeSH terms

  • Animals
  • Astragalus Plant / chemistry*
  • Cytokines / immunology
  • Interleukin-1beta / immunology
  • Intracellular Signaling Peptides and Proteins / immunology*
  • Macrophage Activation / drug effects*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Nitric Oxide / immunology
  • Polysaccharides / chemistry*
  • Polysaccharides / pharmacology*
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Cytokines
  • Interleukin-1beta
  • Intracellular Signaling Peptides and Proteins
  • Polysaccharides
  • TIPE2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide