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

• Published in: Circulation (New York, N.Y.) Vol. 110; no. 20; pp. 3252 - 3258
• Main Authors: Van Lenten, Brian J, Wagner, Alan C, Navab, Mohamad, Anantharamaiah, G M, Hui, Eric Ka-Wai, Nayak, Debi P, Fogelman, Alan M
• Format: Journal Article
• Language: English
• Published: United States 16-11-2004
• Subjects: Adenocarcinoma - pathology; Apolipoprotein A-I; Cell Line, Tumor - metabolism; Cell Line, Tumor - pathology; Cell Line, Tumor - virology; Cysteine Endopeptidases - analysis; Cytokines - analysis; Depression, Chemical; Enzyme Activation - drug effects; Humans; Inflammation - prevention & control; Inflammation - virology; Influenza A virus - physiology; Influenza virus; Interferon-alpha - biosynthesis; Interferon-beta - biosynthesis; Interleukin-6 - biosynthesis; Lipoproteins, LDL - chemistry; Lung Neoplasms - pathology; Oxidation-Reduction; Peptides - pharmacology; Phospholipids - analysis; Pulmonary Alveoli - cytology; Virus Replication - drug effects
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.0000147232.75456.B3

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.
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.
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.