The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-kappa B in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7

Small heterodimer partner (SHP), specifically expressed in liver and a limi ted number of other tissues, is an unusual orphan nuclear receptor that lac ks the conventional DNA binding domain. In this work, we found that SHP exp ression is abundant in murine macrophage cell line RAW 264.7 but was suppre ssed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hyd roxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated re ceptor gamma. Furthermore, SHP acted as a transcription coactivator of nucl ear factor-kappaB (NF kappaB) and was essential for the previously describe d NF kappaB transactivation by palmitoyl lysophosphaticlylcholine, one of t he oxLDL constituents. Accordingly NF kappaB, which was transcriptionally a ctive 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 o f NF kappaB in oxLDL-treated, resting macrophage cells.