Apolipoprotein A-1 Binding Protein Inhibits Inflammatory Signaling Pathways by Binding to Apolipoprotein A-1 in THP-1 Macrophages.

ABSTRACT

BACKGROUND: It has previously been demonstrated that apolipoprotein A-1 (apoA-1) binding protein (AIBP) promotes apoA-1 binding to ATP-binding cassette transporter A1 (ABCA1) and prevents ABCA1 protein degradation so as to inhibit foam cell formation. Because apoA-1 inhibits inflammatory signaling pathways, whether AIBP has an inhibitory effect on inflammatory signaling pathways in THP-1-derived macrophages is investigated.Methods and Results:Analysis of inflammation-related gene expression indicated that AIBP decreased lipopolysaccharide (LPS)-mediated macrophage inflammation. AIBP significantly prevented NF-κB nuclear translocation. Further, AIBP prevented the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular-signal regulated kinase and c-Jun N-terminal kinase. AIBP decreased MyD88 expression at both mRNA and protein levels, but did not have any effect on TLR4 expression. Moreover, treatment with both AIBP and apoA-1 decreased the abundance of TLR4 in the lipid raft fraction. AIBP lacking 115-123 amino acids (∆115-123), however, did not have such effects as described for intact AIBP. In addition, knockdown of ABCA1 inhibited the effects of AIBP on inflammatory factor secretion. CONCLUSIONS: These results suggest that AIBP inhibits inflammatory signaling pathways through binding to apoA-1 and stabilizing ABCA1, and subsequent alteration of lipid rafts and TLR4 in the cell membrane.