TLR-2 is involved in airway epithelial cell response to air pollution particles

Toxicol Appl Pharmacol. 2005 Feb 15;203(1):45-52. doi: 10.1016/j.taap.2004.07.007.


Primary cultures of normal human airway epithelial cells (NHBE) respond to ambient air pollution particulate matter (PM) by increased production of the cytokine IL-8, and the induction of several oxidant stress response genes. Components of ambient air PM responsible for stimulating epithelial cells have not been conclusively identified, although metal contaminants, benzo[a]pyrene and biological matter have been implicated. Stimulation of IL-8 release from NHBE with coarse (PM(2.5-10)), fine (PM2.5), and UF particle fractions has shown that the coarse particle fraction has the greatest effect on the epithelial cells as well as alveolar macrophages (AM). Since this fraction concentrates fugitive dusts and particle-associated microbial matter, it was hypothesized that NHBE may recognize PM through microbial pattern recognition receptors TLR2 and TLR4, as has been previously shown with AM. NHBE were shown to release IL-8 when exposed to a Gram-positive environmental isolate of Staphylococcus lentus, and lower levels when exposed to Gram-negative Pseudomonas spp. Comparison of TLR2 and TLR4 mRNA expression in NHBE and AM showed that NHBE express similar levels of TLR2 mRNA as the AM, but expressed very low levels of TLR4. When NHBE were stimulated with PM(2.5-10), PM2.5, and UF PM, in the presence or absence of inhibitors of TLR2 and TLR4 activation, a blocking antibody to TLR2 inhibited production of IL-8, while TLR4 antagonist E5531 or the LPS inhibitor Polymixin B had no effect. Furthermore, effects on expression of TLR2 and TLR4 mRNA, as well as the stress protein HSP70 was assessed in NHBE exposed to PM. TLR4 expression was increased in these cells while TLR2 mRNA levels were unchanged. Hsp70 was increased by PM(2.5-10) > PM2.5 > UF PM suggesting the possibility of indirect activation of TLR pathway by this endogenous TLR2/4 agonist.

MeSH terms

  • Adolescent
  • Adult
  • Air Pollutants / toxicity*
  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Female
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / biosynthesis*
  • HSP70 Heat-Shock Proteins / genetics
  • Humans
  • Interleukin-8 / biosynthesis
  • Macrophages, Alveolar / drug effects*
  • Macrophages, Alveolar / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Particle Size
  • Pseudomonas / pathogenicity
  • RNA, Messenger / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Staphylococcus / pathogenicity
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Air Pollutants
  • HSP70 Heat-Shock Proteins
  • Interleukin-8
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors