Effects of endocrine active contaminating pesticides on RACK1 expression and immunological consequences in THP-1 cells

Environ Toxicol Pharmacol. 2022 Oct:95:103971. doi: 10.1016/j.etap.2022.103971. Epub 2022 Sep 6.

Abstract

We have previously demonstrated that RACK1, which expression is under steroid hormone control, plays an important role in the activation of immune cells and its expression can be useful to evaluate the immunotoxic profile of endocrine disrupting chemicals (EDCs). Hence, we investigated the effects of three contaminating and persistent pesticides: the fungicide vinclozolin (VIN), the herbicide atrazine (ATR) and the insecticide cypermethrin (CYP) on RACK1 expression and on innate immune response. VIN resulted in modest alteration of RACK1 while ATR and CYP reduced in a dose dependent manner RACK1 expression, ultimately leading to the decrease in lipopolysaccharide-induced IL-8 and TNF-α release and CD86 and CD54 surface marker expression. Moreover, our data indicate that, after exposure to EDCs, alterations of RACK1 expression can also occur with mechanisms not directly mediated by an interaction with a nuclear or membrane steroid receptors. Therefore, RACK1 could represent a useful EDCs screening tool to evaluate their immunotoxic potential and to dissect their mechanisms of action.

Keywords: Atrazine; Cypermethrin; Endocrine disrupting chemicals (EDCs); Immunotoxicity; RACK1; Vinclozolin.

MeSH terms

  • Atrazine* / toxicity
  • Endocrine Disruptors* / toxicity
  • Fungicides, Industrial*
  • Herbicides*
  • Hormones
  • Humans
  • Insecticides*
  • Interleukin-8 / metabolism
  • Lipopolysaccharides
  • Neoplasm Proteins
  • Pesticides* / toxicity
  • Receptors for Activated C Kinase
  • THP-1 Cells
  • Tumor Necrosis Factor-alpha

Substances

  • Endocrine Disruptors
  • Fungicides, Industrial
  • Herbicides
  • Hormones
  • Insecticides
  • Interleukin-8
  • Lipopolysaccharides
  • Neoplasm Proteins
  • Pesticides
  • RACK1 protein, human
  • Receptors for Activated C Kinase
  • Tumor Necrosis Factor-alpha
  • Atrazine