D-4F, an apolipoprotein A-I mimetic peptide, inhibits the inflammatory response induced by influenza A infection of human type II pneumocytes

Academic Article

Abstract

  • Background - Evidence suggests that apolipoprotein A-I (apoA-I) and HDL play important roles in modulating inflammation. We previously reported that an apoA-I mimetic peptide, D-4F, reduced inflammatory responses to influenza virus in mice. To further define the antiinflammatory activity of D-4F, a human alveolar type II cell line, A549, was used. Methods and Results - Cells were either uninfected or infected with influenza A in the presence or absence of D-4F. Cells treated with D-4F were more viable, and virus-induced cytokine production was suppressed by D-4F. Caspases associated with cytokine production were activated after infection but suppressed by D-4F treatment. Infected A549 cells showed dramatic increases in cellular phospholipid secretion into the media. When infected cells were incubated with D-4F, secretion of parent nonoxidized, noninflammatory phospholipids was unaltered, but production of proinflammatory oxidized phospholipids was inhibited. Conclusions - Type II pneumocytes respond to influenza A infection by activating caspases and secreting cytokines and cellular phospholipids into the extracellular environment, including oxidized phospholipids that evoke inflammatory responses. D-4F treatment inhibited these events. Our results suggest that apoA-I and apoA-I mimetic peptides such as D-4F are antiinflammatory agents that may have therapeutic potential.
  • Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Van Lenten BJ; Wagner AC; Navab M; Anantharamaiah GM; Hui EKW; Nayak DP; Fogelman AM
  • Start Page

  • 3252
  • End Page

  • 3258
  • Volume

  • 110
  • Issue

  • 20