[Modulation of inflammatory cytokines by ATP-binding cassette A1 in THP-1 macrophages].
OBJECTIVE
To observe the effects of ATP-binding cassette A1 (ABCA1) on intercellular cell adhesion molecule type 1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and interleukin-1beta (IL-1beta) in THP-1 macrophages stimulated with 8-Br-cAMP to identify a possible new mechanism that ABCA1 contributes to atherosclerogenesis (AS).


METHODS
Monocytic THP-1 cells were cultured in the presence of 100 nmol/L phorbol myristate acetate (PMA) for 72 h to transform the cells into THP-1 macrophages. After the macrophages were stimulated with 8-Br-cAMP (final concentration 0.5 mmol/L) for 3, 6, 12 and 24 h respectively, the amounts of ABCA1, ICAM-1 and MCP-1 mRNA were examined by real-time fluorescent quantitative RT-PCR, and the protein amounts of ABCA1, ICAM-1, MCP-1 and IL-1beta were determined by Western blotting and enzyme-linked immunosorbent assay (ELISA). Phosphorothioate antisense oligonucleotides of ABCA1 were add into the culture media at a final concentration of 100 nmol/L and the experiments were repeated.


RESULTS
ABCA1, ICAM-1 and MCP-1 mRNA and protein and IL-1beta protein were increased in the macrophages after stimulation with 8-Br-cAMP for 6 and 12 h. The mRNA expressions of ABCA1, ICAM-1 and MCP-1 were decreased significantly at 3 and 6 h (P<0.01), and the protein expressions of ABCA1, ICAM-1, MCP-1 and IL-1beta declined significantly at 12 and 24 h (P<0.01) after transfection of the macrophages with antisense oligonucleotides of ABCA1.


CONCLUSIONS
ABCA1 can increase the expressions of the inflammatory cytokines in THP-1 macrophages stimulated by 8-Br-cAMP and plays a role in the pathogenesis of AS.
Guo
Zhi-gang
ZG
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. guodoctor@hotmail.com
Wu
Ping-sheng
PS
Li
Jian-hua
JH
Lai
Wen-yan
WY
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013755:Tetradecanoylphorbol Acetate