Acute Phase Proteins in the Acute Phase Response by J. Gauldie (auth.), M. B. Pepys MA, MD, PhD, FRCP, MCRPath

By J. Gauldie (auth.), M. B. Pepys MA, MD, PhD, FRCP, MCRPath (eds.)

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The study of the effect of monokines on CRP induction has been difficult due to the low level of endogenous CRP expression in hepatoma cells. In contrast, the transfected CRP promoter fused to the CAT gene is highly inducible both in hep3B and hepG2, and in the former at least 10- to 20-fold better than in the latter (Arcone et al. 1988). An explanation for the different behaviour of endogenous and transfected CRP is that the endogenous gene is somehow inactivated, perhaps by altered chromatin configuration or methylation, and it is not accessible to transcription factors.

First, haptoglobin belongs to class II in human cells, but to class I in rat cells. Moreover, several genes like CRP, AGP, ACH and haptoglobin itself are induced by more than one monokine. The assignment to class I or class II is based on the cytokine that gives the higher level of induction. The use of different systems has generated some conflicting results. For example, hepG2 and hep3B respond to IL-6 in a slightly different manner: 34 Transcriptional Regulation of Acute Phase Response Genes haptoglobin synthesis is more sensitive to IL-6 induction in hep3B than in hepG2.

2). 3) (Edbrooke et al. 1989). Since PMA is known to induce nuclear DNA-binding proteins, we performed gel retardation assays to see if PMA also induces a nuclear DNA-binding protein in our system (Edbrooke et al. 1989). 4a demonstrates the induction of nuclear protein from He La cells (known to possess PMA responsive nuclear factor, NFKB) , and from transfected L-cells, binding to the 265 bp promoter fragment of SAA. Moreover, footprint analysis (Fig. 4b) showed that the DNA 23 Cytokine Control of SAA Expression 50 bp -200 -92 -72 II Exon 1 ~ TATA box ~ o

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