Induction of apoptosis by particulate matter: Role of TNF-α and MAPK Academic Article uri icon


MeSH Major

  • Apoptosis
  • Benzo(a)pyrene
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Carbon
  • Macrophages, Peritoneal
  • Mitogen-Activated Protein Kinases
  • Tumor Necrosis Factor-alpha


  • Particulate matter (PM) is a major by-product from the combustion of fossil fuels. The biological target of inhaled PM is the pulmonary epithelium and resident macrophages. In this study, we demonstrate that cultured macrophages (RAW 264.7 cells) exposed continously to a well-defined model of PM [benzo[a]pyrene adsorbed on carbon black (CB+BaP)] exhibit a time-dependent expression and release of the cytokine tumor necrosis factor-alpha (TNF-alpha). CB+BaP also evoked programmed cell death or apoptosis in cultured macrophages as assessed by genomic DNA-laddering assays. The CB+BaP-induced apoptosis was inhibited when macrophages were treated with CB+BaP in the presence of a neutralizing antibody to TNF-alpha, suggesting that TNF-alpha plays an important role in mediating CB+BaP-induced apoptosis in macrophages. Interestingly, neither untreated carbon black nor benzo[a]pyrene alone induced apoptosis or caused the release of TNF-alpha in RAW 264.7 cells. Moreover, we observed that TNF-alpha activates mitogen-activated protein kinase (MAPK) activity, the extracellular signal-regulated kinases p42/p44, in a time-dependent manner. RAW 264.7 cells treated with PD-098059, a selective inhibitor of MAPK kinase activity, did not exhibit CB+BaP-induced apoptosis and TNF-alpha secretion. Furthermore, cells treated with the MAPK kinase inhibitor did not undergo TNF-alpha-induced apoptosis. Taken together, our data suggest that TNF-alpha mediates PM-induced apoptosis and that the MAPK pathway may play an important role in regulating this pathway.

publication date

  • December 7, 1998



  • Academic Article



  • eng

PubMed ID

  • 9815112

Additional Document Info

start page

  • L942

end page

  • 9


  • 275


  • 5 19-5