PMID- 23835648 OWN - NLM STAT- MEDLINE DCOM- 20140612 LR - 20181202 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 30 IP - 3 DP - 2013 Sep TI - Porphyromonas gingivalis lipopolysaccharide increases lipid accumulation by affecting CD36 and ATP-binding cassette transporter A1 in macrophages. PG - 1329-36 LID - 10.3892/or.2013.2600 [doi] AB - Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) promotes macrophage-derived foam cell formation, however, the mechanisms are not well established. In macrophages, lipid uptake is mediated by scavenger receptors including SR-A and CD36, while the cholesterol efflux is mediated by ATP-binding cassette transporter G1 (ABCG1), ABCA1 and SR-BI. We further investigated the mechanisms underlying the dysregulation by P. gingivalis LPS of these regulators resulting in the promotion of lipid accumulation in THP-1-derived macrophages. Our results showed that P. gingivalis LPS exacerbated lipid accumulation in oxidized low-density lipoprotein (oxLDL)-treated macrophages. However, cholesterol efflux was inhibited by P. gingivalis LPS in THP-1-derived macrophages. In oxLDL-untreated macrophages, P. gingivalis LPS treatment caused an increase in CD36 mRNA and protein levels, and a decrease in ABCA1 mRNA and protein levels, while having no effect on SR-A, SR-BI or ABCG1 expression. Upregulation of CD36 by P. gingivalis LPS resulted from activation of c-Jun/AP-1, and this was confirmed by the inhibition of increased CD36 expression after AP-1 inhibition using SP600125. However, the decreased protein stability of ABCA1 by P. gingivalis LPS was a result of increased calpain activity. Moreover, small hairpin RNA (shRNA) targeting heme oxygenase-1 (HO-1) augmented the P. gingivalis LPS-induced atherogenic effects on the expression of c-Jun/AP-1, CD36, ABCA1 and calpain activity. Accordingly, P. gingivalis LPS-regulated promotion of lipid accumulation in foam cells was also exacerbated by HO-1 shRNA. These results indicate that P. gingivalis LPS confers a exacerbation effect on the formation of foam cells by a novel HO-1-dependent mediation of cholesterol efflux and lipid accumulation in macrophages. FAU - Li, Xiu-Ying AU - Li XY AD - Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China. FAU - Wang, Chun AU - Wang C FAU - Xiang, Xue-Rong AU - Xiang XR FAU - Chen, Fang-Chun AU - Chen FC FAU - Yang, Cong-Ming AU - Yang CM FAU - Wu, Jing AU - Wu J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130708 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (ABCG1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (CD36 Antigens) RN - 0 (Lipopolysaccharides) RN - 0 (Lipoproteins, LDL) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (oxidized low density lipoprotein) RN - 97C5T2UQ7J (Cholesterol) RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/genetics/*metabolism MH - Blotting, Western MH - CD36 Antigens/genetics/*metabolism MH - Cells, Cultured MH - Cholesterol/*metabolism MH - Foam Cells/drug effects MH - Heme Oxygenase-1/antagonists & inhibitors/genetics/metabolism MH - Humans MH - Immunoprecipitation MH - Lipid Metabolism/*drug effects MH - Lipopolysaccharides/*pharmacology MH - Lipoproteins, LDL/pharmacology MH - Macrophages/cytology/drug effects/*metabolism MH - Porphyromonas gingivalis/*chemistry MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2013/07/10 06:00 MHDA- 2014/06/13 06:00 CRDT- 2013/07/10 06:00 PHST- 2013/05/10 00:00 [received] PHST- 2013/06/19 00:00 [accepted] PHST- 2013/07/10 06:00 [entrez] PHST- 2013/07/10 06:00 [pubmed] PHST- 2014/06/13 06:00 [medline] AID - 10.3892/or.2013.2600 [doi] PST - ppublish SO - Oncol Rep. 2013 Sep;30(3):1329-36. doi: 10.3892/or.2013.2600. Epub 2013 Jul 8.