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 gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappaB (NF kappaB) and was essential for the previously described NF kappaB transactivation by palmitoyl lysophosphaticlylcholine, one of the oxLDL constituents. Accordingly NF kappaB, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SBP appears to be an important modulatory component to regulate the transcriptional activities of NF kappaB in oxLDL-treated, resting macrophage cells.