Molecular cloning and characterization of mouse LITAF cDNA: role in the regulation of tumor necrosis factor-α (TNF-α) gene expression

Abstract

The inflammatory response to bacteria and bacterial products, such as lipopolysaccharides (LPSs), is mediated by a variety of secreted factors, but cytotoxic effects of LPS have been ascribed to the tumor necrosis factor alpha (TNF-α) activity. TNF-α is probably the most pleiotropic cytokine and, given the deleterious effects to the host of this factor, it has been postulated that its expression must be tightly regulated. Our laboratory has recently isolated, cloned and characterized a novel human transcription factor named LITAF or LPS-induced TNF-alpha factor. The present study reports the isolation, cloning and characterization of the mouse LITAF cDNA. Chromosomal localization revealed that mouse LITAF mapped to mouse chromosome 16, in a region highly homologous with the area on which human LITAF was previously located. Northern blot analysis shows that mouse LITAF is already expressed at embryonic day 7 of development, and is highly expressed in adult liver, heart and kidney. Moreover, upon LPS stimulation, we show that: (i) LITAF expression is increased in a mouse monocyte/macrophage cell line; and (ii) TNF-α expression is reduced in ES cell-derived macrophages lacking one copy of LITAF gene. Taken together, these results highlight the important role of LITAF in the regulation of TNF-α gene expression and suggest a potential role of LITAF in mouse organogenesis.

Keywords

Inflammation monocytes/macrophages lipopolysaccharide gene regulation LITAF

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