摘要
Interleukin-18 (IL-18) is a pleiotropic cytokine involved in the development of T helper type 1 (Thl) cells, and it plays important roles in regulation of both the innate and acquired immune responses. The aim of this study was to elucidate whether the reversible histone acetylation/ deacetylation modification participates in the regulation of IL-18 transcription expression. The transcription coactivator p300 containing the histone acetyltransferase (HAT) activity, and the histone deacetylase 3 (HDAC3) were used in this study to analyze the effect of this modification in the regula-tion of mouse IL-18 gene. The results demonstrate that transfection of p300-expression plasmid promotes the en-dogenous IL-18 mRNA synthesis in J774 cells, and stimulates the activation of IL-18 promoter. It has been found that this stimulating effect of p300 was reversed by HDAC3, indicat-ing the involvement of the reversible histone acetyla-tion/deacetylation modification in IL-18 regulation. Fur-thermore, the data show that the HAT activity of p300 was essential to its function in activating IL-18 promoter. In ad-dition, p300 was shown to be able to work synergistically with the transcription factor c-Fos on activation of IL-18 promoter and this effect could also be impaired by HDAC3. Results presented in this paper indicate that the reversible histone acetylation/deacetylation modification plays an im-portant role in the transcriptional regulation of IL-18.
Interleukin-18 (IL-18) is a pleiotropic cytokine involved in the development of T helper type 1 (Thl) cells, and it plays important roles in regulation of both the innate and acquired immune responses. The aim of this study was to elucidate whether the reversible histone acetylation/ deacetylation modification participates in the regulation of IL-18 transcription expression. The transcription coactivator p300 containing the histone acetyltransferase (HAT) activity, and the histone deacetylase 3 (HDAC3) were used in this study to analyze the effect of this modification in the regula-tion of mouse IL-18 gene. The results demonstrate that transfection of p300-expression plasmid promotes the en-dogenous IL-18 mRNA synthesis in J774 cells, and stimulates the activation of IL-18 promoter. It has been found that this stimulating effect of p300 was reversed by HDAC3, indicat-ing the involvement of the reversible histone acetyla-tion/deacetylation modification in IL-18 regulation. Fur-thermore, the data show that the HAT activity of p300 was essential to its function in activating IL-18 promoter. In ad-dition, p300 was shown to be able to work synergistically with the transcription factor c-Fos on activation of IL-18 promoter and this effect could also be impaired by HDAC3. Results presented in this paper indicate that the reversible histone acetylation/deacetylation modification plays an im-portant role in the transcriptional regulation of IL-18.
