The role and regulation of the anti-inflammatory mouse apolipoprotein J gene.

摘要

Apolipoprotein J (apoJ) is a secreted protein with chaperone homology found in vertebrates and is induced and deposited in both physiologic and pathologic states. ApoJ is hypothesized to be a novel extracellular heat shock protein. I characterized the stress response regulation of the mouse apoJ gene. Cell culture experiments verified the essential roles of an apoJ promoter heat shock element (HSE) and the heat shock transcription factor 1 (HSF 1) in heat shock-dependent apoJ gene activation. My studies identified multiple cooperating cis-elements, including a promoter activator protein-1 (AP-1) binding motif, an intron 1 enhancer, and a downstream silencer, that together conferred the full range of apoJ gene expression. I also sought to determine the function of the mouse apoJ gene in response to immune complex-mediated glomerulonephritis. I observed that apoJ deficiency exacerbated renal inflammation and predisposed to rapidly progressive disease. My data also revealed that apoJ levels affected the differentiation of the immune response. These experiments establish apoJ as a highly evolved heat shock protein that suppresses inflammation and immune-mediated tissue injury.