title: FABP5 deficiency enhances susceptibility to H1N1 influenza A virus-induced lung inflammation.
abstract: The early inflammatory response to influenza A virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which inflammatory cells invade the respiratory tract remain unclear. Uncontrolled inflammation and oxidative stress cause lung damage in response to influenza A infection. We have previously shown that the fatty acid binding protein 5 (FABP5) has anti-inflammatory properties. We speculate that, as a transporter of fatty acids, FABP5 plays an important protective role against oxidative damage to lipids during infection as well. Using FABP5-/- and wild-type (WT) mice infected with influenza A virus, we showed that FABP5-/- mice had increased cell infiltration of macrophages and neutrophils compared with WT mice. FABP5-/- mice presented lower viral burden but lost as much weight as WT mice. The adaptive immune response was also increased in FABP5-/- mice as illustrated by the accumulation of T and B cells in the lung tissues and increased levels of H1N1-specific IgG antibodies. FABP5 deficiency greatly enhanced oxidative damage and lipid peroxidation following influenza A infection and presented with sustained tissue inflammation. Interestingly, FABP5 expression decreased following influenza A infection in WT lung tissues that corresponded to a decrease in the anti-inflammatory molecule PPAR-γ activity. In conclusion, our results demonstrate a previously unknown contribution of FABP5 to influenza A virus pathogenesis by controlling excessive oxidative damage and inflammation. This property could be exploited for therapeutic purposes.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gally
authors.forename: Beata
authors.initials: B
authors.lastname: Kosmider
authors.forename: Michael R
authors.initials: MR
authors.lastname: Weaver
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Pate
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Oberley-Deegan
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology* / Q000821:virology; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000502:physiology*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D047495:PPAR gamma; D012333:RNA, Messenger
keywords: FABP5; inflammation; influenza A; lipid peroxidation