Gene Expression Profiling and Network Analysis Reveals Lipid and Steroid Metabolism to Be the Most Favored by TNFα in HepG2 Cells

BACKGROUND: The proinflammatory cytokine, TNFα, is a crucial mediator of the pathogenesis of several diseases, more so in cases involving the liver wherein it is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Gene expression profiling serves as an appropriate strategy to unravel the underlying signatures to envisage such varied responses and considering this, gene transcription profiling was examined in control and TNFα treated HepG2 cells. METHODS AND FINDINGS: Microarray experiments between control and TNFα treated HepG2 cells indicated that TNFα could significantly alter the expression profiling of 140 genes; among those up-regulated, several GO (Gene Ontology) terms related to lipid and fat metabolism were significantly (p<0.01) overrepresented indicating a global preference of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in several aspects of the immune response like immunoglobulin receptor activity and IgE binding thereby indicating a compromise in the immune defense mechanism(s). Conserved transcription factor binding sites were identified in identically clustered genes within a common GO term and SREBP-1 and FOXJ2 depicted increased occupation of their respective binding elements in the presence of TNFα. The interacting network of “lipid metabolism, small molecule biochemistry” was derived to be significantly overrepresented that correlated well with the top canonical pathway of “biosynthesis of steroids”. CONCLUSIONS: TNFα alters the transcriptome profiling within HepG2 cells with an interesting catalog of genes being affected and those involved in lipid and steroid metabolism to be the most favored. This study represents a composite analysis of the effects of TNFα in HepG2 cells that encompasses the altered transcriptome profiling, the functional analysis of the up- and down- regulated genes and the identification of conserved transcription factor binding sites. These could possibly determine TNFα mediated alterations mainly the phenotypes of hepatic steatosis and fatty liver associated with several hepatic pathological states.