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


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.
Van Lenten
Brian J
BJ
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-1679, USA. bvanlent@mednet.ucla.edu
Wagner
Alan C
AC
Navab
Mohamad
M
Anantharamaiah
G M
GM
Hui
Eric Ka-Wai
EK
Nayak
Debi P
DP
Fogelman
Alan M
AM
D000230:Adenocarcinoma / Q000473:pathology; D016632:Apolipoprotein A-I; D045744:Cell Line, Tumor / Q000378:metabolism / Q000473:pathology / Q000821:virology; D003546:Cysteine Endopeptidases / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003864:Depression, Chemical; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control* / Q000821:virology; D009980:Influenza A virus / Q000502:physiology*; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000737:chemistry; D008175:Lung Neoplasms / Q000473:pathology; D010084:Oxidation-Reduction; D010455:Peptides / Q000494:pharmacology*; D010743:Phospholipids / Q000032:analysis; D011650:Pulmonary Alveoli / Q000166:cytology*; D014779:Virus Replication / Q000187:drug effects
D016632:Apolipoprotein A-I; D016207:Cytokines; C465468:D-4F peptide; D016898:Interferon-alpha; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D010455:Peptides; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D016899:Interferon-beta; D003546:Cysteine Endopeptidases