PMID- 25953328 OWN - NLM STAT- Publisher LR - 20240227 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) DP - 2015 May 7 TI - Protein Kinase C Is Involved in the Induction of ATP-Binding Cassette Transporter A1 Expression by Liver X Receptor/Retinoid X Receptor Agonist in Human Macrophages. LID - 10.1002/jcp.25157 [doi] AB - The transcription of the ATP-binding cassette transporter A1 (ABCA1) gene, which plays a key anti-atherogenic role, is known to be induced by agonists of liver X receptors (LXRs). LXRs form obligate heterodimers with retinoid X receptors (RXRs) and interact with their recognition sequences in the regulatory regions of key genes implicated in the control of cholesterol, fatty acid and glucose homeostasis. We have previously shown a novel role for c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K) in the LXRs-mediated induction of macrophage gene expression. Protein kinase C (PKC) is often found to regulate the action of nuclear receptors and cross talk between this kinase family and JNK and/or PI3K has been shown in several settings. We have therefore investigated a potential role for PKC in the action of LXR/RXR agonist 22-(R)-hydroxycholesterol (22-(R)-HC)/9-cis-retinoic acid (9cRA) in THP-1 macrophages, including the induction of ABCA1 expression. The pan PKC inhibitor bisindoylmaleimide was found to attenuate the induction of ABCA1 protein expression, the activation of the JNK signaling pathway and the stimulation of activator protein-1 (AP-1) DNA binding activity in macrophages treated with 22-(R)-HC and 9cRA. The role of PKC in the action of these ligands was confirmed further by the use of more isotype-specific inhibitors. These studies therefore reveal a potentially important role for PKC in the action of 22-(R)-HC and 9cRA in human macrophages. This article is protected by copyright. All rights reserved. CI - This article is protected by copyright. All rights reserved. FAU - Huwait, Etimad A AU - Huwait EA AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. FAU - Singh, Nishi N AU - Singh NN AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. FAU - Michael, Daryn R AU - Michael DR AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. FAU - Davies, Thomas S AU - Davies TS AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. FAU - Moss, Joe W E AU - Moss JW AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. FAU - Ramji, Dipak P AU - Ramji DP AD - Cardiff School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, United Kingdom. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20150507 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RIN - J Cell Physiol. 2016 Apr;231(4):964. PMID: 27392327 OTO - NOTNLM OT - Atherosclerosis OT - Cell Signaling OT - Gene Expression OT - Liver X Receptors OT - Macrophages OT - Nuclear Receptors EDAT- 2015/05/09 06:00 MHDA- 2015/05/09 06:00 CRDT- 2015/05/09 06:00 PHST- 2014/07/03 00:00 [received] PHST- 2015/02/10 00:00 [revised] PHST- 2015/03/03 00:00 [accepted] PHST- 2015/05/09 06:00 [entrez] PHST- 2015/05/09 06:00 [pubmed] PHST- 2015/05/09 06:00 [medline] AID - 10.1002/jcp.25157 [doi] PST - aheadofprint SO - J Cell Physiol. 2015 May 7. doi: 10.1002/jcp.25157.