Abstract
Interleukin‐18 (IL‐18), an important regulator of innate and acquired immune responses expressed from a variety of cell types, is a pleiotropic cytokine in the development of T helper type 1 (Thl) cells. The p300/CBP (CREB‐binding protein) coactivator proteins are important histone acetyltransferases (HATs) that regulate the transcription of many genes. Whether p300/CBP play a role in the IL‐18 expression has not been investigated previously. In this study, we analyzed the roles of p300 in the regulation of mouse IL‐18 by using RT‐PCR and a series of co‐transfection studies. We showed that p300 had a stimulating effect on the endogenous IL‐18 mRNA synthesis and on the activity of IL‐18 p1 promoter. The results also showed that IL‐18 p1 promoter activity was enhanced by p300 in a dose‐dependent manner. Moreover, the p300‐mediated activation function can be suppressed by the adenovirus E1A protein, which inhibits the HAT function of p300. Also, a mutation in p300 HAT region abolished the effect of p300 on IL‐18 activation. These data further indicate that the acetylase activity of p300 was indispensable to its function. Furthermore, we found that p300 was able to enhance the effect of the transcription factor c‐Fos on activation of the IL‐18 promoter. Data presented in this paper implicate important roles of p300 in the transcriptional regulation of IL‐18. © 2004 Wiley‐Liss, Inc.