Induction of apoptosis by particulate matter: Role of TNF-α and MAPK

Beek Yoke Chin, Mary E. Choi, Marie D. Burdick, Robert M. Strieter, Terence H. Risby, Augustine M.K. Choi

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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[α]pyrene adsorbed on carbon black (CB+BaP)] exhibit a time- dependent expression and release of the cytokine tumor necrosis factor-α (TNF-α). 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-α, suggesting that TNF-α 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-α in RAW 264.7 cells. Moreover, we observed that TNF-α 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-α secretion. Furthermore, cells treated with the MAPK kinase inhibitor did not undergo TNF-α-induced apoptosis. Taken together, our data suggest that TNF-α mediates PM-induced apoptosis and that the MAPK pathway may play an important role in regulating this pathway.

Original languageEnglish (US)
Pages (from-to)L942-L949
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number5 19-5
DOIs
StatePublished - 1998

Keywords

  • Carbon
  • Cytokines
  • Macrophages
  • Mitogen-activated protein kinase
  • Programmed cell death
  • Signal transduction
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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