title: PLTP regulates STAT3 and NFκB in differentiated THP1 cells and human monocyte-derived macrophages.
abstract: Phospholipid transfer protein (PLTP) plays an important role in regulation of inflammation. Previously published studies have shown that PLTP binds, transfers and neutralizes bacterial lipopolysaccharides. In the current study we tested the hypothesis that PLTP can also regulate anti-inflammatory pathways in macrophages. Incubation of macrophage-like differentiated THP1 cells and human monocyte-derived macrophages with wild-type PLTP in the presence or absence of tumor necrosis factor alpha (TNFα) or interferon gamma (IFNγ) significantly increased nuclear levels of active signal transducer and activator of transcription 3, pSTAT3(Tyr705) (p<0.01). Similar results were obtained in the presence of a PLTP mutant without lipid transfer activity (PLTP(M159E)), suggesting that PLTP-mediated lipid transfer is not required for activation of the STAT3 pathway. Inhibition of ABCA1 by chemical inhibitor, glyburide, as well as ABCA1 RNA inhibition, reversed the observed PLTP-mediated activation of STAT3. In addition, PLTP reduced nuclear levels of active nuclear factor kappa-B (NFκB) p65 and secretion of pro-inflammatory cytokines in conditioned media of differentiated THP1 cells and human monocyte-derived macrophages. Our data suggest that PLTP has anti-inflammatory capabilities in macrophages.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. simona@uw.edu
authors.forename: S
authors.initials: S
authors.lastname: Vuletic
authors.forename: W
authors.initials: W
authors.lastname: Dong
authors.forename: G
authors.initials: G
authors.lastname: Wolfbauer
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: J J
authors.initials: JJ
authors.lastname: Albers
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D001692:Biological Transport / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D016328:NF-kappa B; C493430:PLTP protein, human; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D005905:Glyburide