The Effects of Agaricus blazei Murill Polysaccharides on Cadmium-Induced Apoptosis and the TLR4 Signaling Pathway of Peripheral Blood Lymphocytes in Chicken

Biol Trace Elem Res. 2017 Nov;180(1):153-163. doi: 10.1007/s12011-017-0969-3. Epub 2017 Mar 10.

Abstract

In this study, we investigated the effects of Agaricus blazei Murill polysaccharides (ABP) on cadmium (Cd)-induced apoptosis and the TLR4 signaling pathway of chicken peripheral blood lymphocytes (PBLs). Seven-day-old healthy chickens were randomly divided into four groups, and each group contained 20 males. The cadmium-supplemented diet group (Cd group) was fed daily with full feed that contained 140 mg cadmium chloride (CdCl2)/kg and 0.2 mL saline. The A. blazei Murill polysaccharide diet group (ABP group) was fed daily with full feed with 0.2 mL ABP solution (30 mg/mL) by oral gavage. The cadmium-supplemented plus A. blazei Murill polysaccharide diet group (Cd + ABP group) was fed daily with full feed containing 140 mg CdCl2/kg and 0.2 mL ABP solution (30 mg/mL) by gavage. The control group was fed daily with full feed with 0.2 mL saline per day. We measured the apoptosis rate and messenger RNA (mRNA) levels of apoptosis genes (caspase-3, Bax, and Bcl-2), the mRNA levels of TLR4 and TLR4 signaling pathway-related factors (MyD88, TRIF, NF-κB, and IRF3), the TLR4 protein expression, and the concentrations of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in chicken PBLs. The results showed that the PBL apoptosis rate was significantly increased, the mRNA levels of caspase-3 and Bax were significantly increased, while that of Bcl-2 was significantly reduced. The Bax/Bcl-2 ratio was significantly increased in the Cd group at 20, 40, and 60 days after treatment compared with that in the control group. After treatment with ABP, the above changes were clearly suppressed. At the same time, ABP reduced the concentrations of IL-1β, IL-6, and TNF-α induced by Cd. We also found that ABP inhibited the TLR4 mRNA level and protein expression and inhibited the mRNA levels of MyD88, TRIF, NF-κB, and IRF3. The results demonstrated that Cd could induce apoptosis, activate the TLR4 signaling pathway, and induce the expression of inflammatory cytokines in chicken PBLs, and that the administration of ABP clearly inhibited Cd-induced effects on chicken PBLs.

Keywords: ABP; Apoptosis; Cadmium; Chicken PBLs; TLR4 signaling pathway.

MeSH terms

  • Agaricus / chemistry*
  • Animals
  • Apoptosis / drug effects
  • Cadmium / toxicity*
  • Caspase 3 / genetics
  • Chickens
  • Cytokines / metabolism
  • Fungal Polysaccharides / pharmacology*
  • Gene Expression Regulation / drug effects
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • bcl-2-Associated X Protein / genetics

Substances

  • Cytokines
  • Fungal Polysaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • Toll-Like Receptor 4
  • bcl-2-Associated X Protein
  • Cadmium
  • Caspase 3