Characterization of a novel PMA-inducible pathway of interleukin-13 gene expression in T cells
Article first published online: 25 OCT 2005
Volume 117, Issue 1, pages 29–37, January 2006
How to Cite
Keen, J. C., Cianferoni, A., Florio, G., Guo, J., Chen, R., Roman, J., Wills-Karp, M., Casolaro, V. and Georas, S. N. (2006), Characterization of a novel PMA-inducible pathway of interleukin-13 gene expression in T cells. Immunology, 117: 29–37. doi: 10.1111/j.1365-2567.2005.02260.x
- Issue published online: 25 OCT 2005
- Article first published online: 25 OCT 2005
- Received 21 December 2004; revised 25 July 2005; accepted 22 August 2005.
- interleukin 13;
- protein kinase C;
- T lymphocyte;
- transcriptional regulation
Although interleukin 13 (IL-13) is an important mediator of asthma and allergic diseases, the molecular mechanisms regulating IL-13 gene expression are not well understood. This study was designed to define the molecular mechanisms governing IL-13 gene expression in T cells. IL-13 expression was examined in human peripheral blood T cells and in the EL-4 T-cell line by enzyme-linked immunosorbent assay and reverse-transcription polymerase chain reaction. An IL-13 promoter deletion analysis was performed using luciferase-based reporter plasmids transiently transfected into EL-4 cells by electroporation. DNA binding factors were investigated using electrophoretic mobility shift assays. In contrast to IL-4 expression, which required concomitant activation of calcium- and protein kinase C- (PKC-) dependent signalling pathways, PKC activation alone was sufficient for IL-13 protein secretion in mitogen-primed (but not resting) peripheral blood T cells, and for IL-13 mRNA expression and promoter activity in EL-4 T cells. Promoter deletion analysis localized a phorbol 12-myristate 13-acetate (PMA) -sensitive element to a proximal promoter region between − 109 and − 79 base pairs upstream from the IL-13 transcription start site. This promoter region supported the binding of both constitutive and PMA-inducible nuclear factors in gel shift assays.