Tumor Necrosis Factor- α Mediates Lipopolysaccharide-Induced Macrophage Inflammatory Protein-2 Release from Alveolar Epithelial Cells Academic Article uri icon

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abstract

  • Our recent studies have demonstrated that in response to lipopolysaccharide (LPS) challenge, alveolar epithelial cells produced tumor necrosis factor (TNF)-alpha, an early response cytokine in the inflammatory process. To investigate whether LPS-induced TNF-alpha release is related to other inflammatory mediators from the same cell type, we examined effects of LPS stimulation on macrophage inflammatory protein (MIP)-2 production by alveolar epithelial cells, and then examined the relationship between TNF-alpha and MIP-2 production. LPS stimulation induced a dose- and time-dependent release of MIP-2. The steady-state messenger RNA level of MIP-2 was significantly increased, with the MIP-2 protein localized within alveolar epithelial cells, as determined by confocal microscopy. The LPS-induced MIP-2 production is regulated at both the transcriptional and post-transcriptional levels. TNF-alpha also induced MIP-2 production from alveolar epithelial cells. Preincubation with an antisense oligonucleotide against TNF-alpha inhibited LPS-induced TNF-alpha in a dose-dependent and sequence-specific manner. The same antisense also inhibited MIP-2 production. The inhibitory effects were highly correlated. Polyclonal and monoclonal antibodies against TNF-alpha also attenuated LPS-induced MIP-2. These results suggest that LPS-induced MIP-2 release from alveolar epithelial cells may be mediated in part by TNF-alpha from the same cell type. This autoregulatory mechanism may amplify LPS-induced signals involved in host defense as well as in acute inflammatory reactions.

authors

  • Xavier, Alexandre M
  • Isowa, Noritaka
  • Cai, Lu
  • Dziak, Ewa
  • Opas, Michal
  • McRitchie, Donna I
  • Slutsky, Arthur S
  • Keshavjee, Shafique
  • Liu, Mingyao

publication date

  • October 1999

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