Polychlorinated Biphenyls (PCB 101, 153, and 180) Impair Murine Macrophage Responsiveness to Lipopolysaccharide: Involvement of NF-κB Pathway

Toxicol Sci. 2015 Sep;147(1):255-69. doi: 10.1093/toxsci/kfv127. Epub 2015 Jul 3.


Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are persistent organic pollutants, associated with a range of adverse health effects, including interference with the immune system. In this study, we investigate the capability of NDL-PCBs 101, 153, and 180, 3 of the 6 NDL-PCBs defined as indicators, to impair the immune response in lipopolysaccharide (LPS)-activated J774A.1 and primary murine macrophages. Our results clearly demonstrate that the exposure of J774A.1 and primary macrophages to NDL-PCB 153 or 180 or all NDL-PCBs mixtures causes a significant reduction in LPS-induced cytokine/chemokine synthesis, such as tumor necrosis factor-α and interleukin-6, together with monocyte chemoattractant protein-1, involved in cell recruitment. Moreover, PCBs were found to suppress LPS-stimulated NO production, and to reduce cyclooxygenase-2 and inducible nitric oxide synthase expression in J774A.1 and primary macrophages. At mechanistic level, PCBs significantly counteract the LPS-driven toll-like receptor (TLR) 4 and CD14 upregulation, therefore inhibiting downstream nuclear factor-κB (NF-κB) activation in J774A.1. Furthermore, PCBs determine a significant loss of macrophage endocytic capacity, a prerequisite for efficient antigen presentation. Taken together, these data indicate that NDL-PCBs reduce macrophage responsiveness, particularly when they are combined at concentrations per se inactive, impairing the capability to orchestrate a proper immune response to an infectious stimulus, disrupting TLR4/NF-κB pathway.

Keywords: NF-κB, toll-like receptor 4; endocytosis; immune suppression; lipopolysaccharide; non-dioxin-like polychlorinated biphenyls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Chemokines / biosynthesis
  • Cyclooxygenase 2 / metabolism
  • Cytokines / biosynthesis
  • Endocytosis / drug effects
  • Environmental Pollutants / toxicity*
  • Lipopolysaccharide Receptors / biosynthesis
  • Lipopolysaccharide Receptors / drug effects
  • Lipopolysaccharides / pharmacology*
  • Macrophage Activation / drug effects
  • Macrophages / drug effects*
  • Male
  • NF-kappa B / drug effects*
  • Nitric Oxide / metabolism
  • Polychlorinated Biphenyls / toxicity*
  • Primary Cell Culture
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / biosynthesis
  • Toll-Like Receptor 4 / drug effects


  • Chemokines
  • Cytokines
  • Environmental Pollutants
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • NF-kappa B
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Nitric Oxide
  • Polychlorinated Biphenyls
  • Cyclooxygenase 2