KMID : 0620920100420050366
|
|
Experimental & Molecular Medicine 2010 Volume.42 No. 5 p.366 ~ p.375
|
|
Involvement of MITF-A, an alternative isoform of mi transcription factor, on the expression of tryptase gene in human mast cells
|
|
Lee Sun-Hee
Lee Jeong-Heon Lee Young-Mi Kim Dae-Ki
|
|
Abstract
|
|
|
Mast cells play a central role in the initiation and development of allergic diseases through release of various mediators. Tryptase has been known to be a key mediator in mast cell-mediated inflammatory reactions. In the present study, we investigated whether the transcription of tryptase gene in human mast cells was induced by microphthalmia (mi)-associated transcription factor (MITF). We observed that the human CD34+ progenitor-derived cultured mast cells and human mast cell line HMC-1 expressed strongly the transcripts of tryptase-beta1 and MITF-A, which is a MITF alterative splicing isoform. The transcriptional activity of tryptase gene was specifically higher in HMC-1 cells compared to the tryptase-negative cells. Using mutant constructs of tryptase promoter, we observed that two E-box (CANNTG) motifs including between -817 to -715 and -421 to -202 are able to involve in the transactivation of tryptase gene by MITF-A. In addition, the binding of these motifs-containing oligonucleotides to MITF proteins was detectable by EMGA using the nuclear extracts of HMC-1 cells and anti-MITF mAb. The overexpression of MITF-A elevated tryptase production by HMC-1 cells, while the introduction of specific siRNA against MITF attenuated the expression and enzymatic activity of tryptase. These data suggest that MITF might play a role in regulating the transcription of tryptase gene in human mast cells.
|
|
KEYWORD
|
|
alternative splicing, gene expression regulation, mast cells, microphthalmia-associated transcription factor, tryptases
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|