The Orphan Nuclear Receptor Small Heterodimer Partner as a Novel Coregulator of Nuclear Factor-κB in Oxidized Low Density Lipoprotein-treated Macrophage Cell Line RAW 264.7

Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor γ. Furthermore, SHP acted as a transcription coactivator of nuclear factor-κB (NFκB) and was essential for the previously described NFκB transactivation by palmitoyl lysophosphatidylcholine, one of the oxLDL constituents. Accordingly NFκB, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SHP appears to be an important modulatory component to regulate the transcriptional activities of NFκB in oxLDL-treated, resting macrophage cells.