Effect of Lead (Pb) on Inflammatory Processes in the Brain

Int J Mol Sci. 2016 Dec 19;17(12):2140. doi: 10.3390/ijms17122140.

Abstract

That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7. A significant role in the development of inflammatory processes in the brain is also played by microglia (residual macrophages in the brain and the spinal cord), which act as the first line of defense in the central nervous system, and astrocytes-Whose most important function is to maintain homeostasis for the proper functioning of neurons. In this paper, we also present evidence that exposure to Pb may result in micro and astrogliosis by triggering TLR4-MyD88-NF-κB signaling cascade and the production of pro-inflammatory cytokines.

Keywords: brain; inflammatory processes; lead (Pb).

Publication types

  • Review

MeSH terms

  • Animals
  • Astrocytes / immunology
  • Astrocytes / pathology*
  • Brain / pathology*
  • Caspase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Humans
  • Inflammation / chemically induced*
  • Inflammation / immunology
  • Lead / toxicity*
  • Mice
  • Microglia / immunology
  • Microglia / pathology*
  • Nitric Oxide Synthase Type II / metabolism
  • Peptide Hydrolases / metabolism
  • Rats
  • Receptors, Purinergic / metabolism
  • Signal Transduction / drug effects

Substances

  • Cytokines
  • Receptors, Purinergic
  • Lead
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Peptide Hydrolases
  • Caspase 1