The human intracellular interleukin 1 receptor antagonist promoter appropriately regulates gene expression in keratinocytes and gastrointestinal epithelial cells in vivo

The 4555-bp promoter fragment for intracellular interleukin 1 receptor anta gonist (4555-bp icIL-1Ra) has recently been demonstrated to regulate gene e xpression in a cell-type specific manner in vitro in transient transfection studies. To examine the activity of this promoter in vivo, transgenic mice possessing the 4555-bp promoter coupled to the E. coli lacZ reporter gene were created. Expression of endogenous icIL-1Ra and E. coli lacZ mRNA were examined in different tissues by RT-PCR, RNase protection assay and in situ hybridization, In transgenic mice both endogenous icIL-1Ra and E. coli lac Z were co-expressed by keratinocytes and by epithelial cells in different o rgans of the digestive system. The transgene was also expressed in the brai n in four out of five lines, whereas endogenous icIL-1Ra was not detected i n this organ. In contrast, only icIL-1Ra mRNA, but not E. coli lacZ mRNA, w as detected in lipopolysaccharide (LPS)-stimulated resident peritoneal macr ophages from icIL-1Ra promoter transgenic mice. These results indicate that a 4555-bp promoter fragment of human icIL-1Ra appropriately regulates gene transcription in keratinocytes and gastrointestinal epithelial cells in vi vo. However, other as yet unidentified regulatory regions influence icIL-1R a gene expression in macrophages following LPS stimulation. (C) 1999 Academ ic Press.