Elucidation of the molecular mechanisms of acute phase protein gene expression regulated by interleukin-6 via peroxisome proliferated activated receptor a and CCAAT/enhancer binding proteins in human liver cells.

Abstract

The acute phase response (APR) is an orchestrated response to tissue injury and infection. A prominent feature of APR is the changes in the expression of liver’s proteins, known as acute phase proteins (APPs). It has been reported that IL-6 signalling regulate the activity of transcription factors including PPARα and C/EBPs which in turn, changes the pattern of APP gene expression. However, transcriptional regulation of APP by IL-6 via these transcription factors is not fully understood. Therefore, the aim of this study was to elucidate the molecular mechanisms of PPARα and C/EBP in mediating IL-6-regulated gene expression of APPs. The effects of transcription factors knockdown on the levels of APP mRNA displayed different pattern of changes upon PPARα and C/EBP knockdown with respective small interference RNA (siRNA). Therefore, the results indicated that PPARα and C/EBP members may have different mechanisms of action in modulating the effects of IL-6 on the gene expression of different APPs in HepG2 cells. This might be due to the diverse arrangements of transcription factor binding elements in different APP promoters as predicted using MatInspector.