Inhibition of transcription factor specificity protein 1 alters the gene expression profile of keratinocytes leading to upregulation of kallikrein-related peptidases and thymic stromal lymphopoietin.
作者： Lianghua Bin , Byung E. Kim , Clifton F. Hall , Sonia M. Leach , Donald Y.M. Leung
DOI: 10.1038/JID.2011.202
关键词:
摘要: Transcription factor specificity protein 1 (Sp1) is involved in diverse cellular functions. We recently found that Sp1 was significantly decreased skin biopsy samples obtained from patients with atopic dermatitis (AD) and had an even greater reduction AD a history of eczema herpeticum. In the current study, we sought to better understand role biological processes by using small-interfering RNA (siRNA) technique knock down gene expression normal human keratinocytes (NHKs) investigated genome-wide profiling Sp1-silenced NHKs. The arrays revealed 53 genes than 3-fold changes NHKs as compared scrambled siRNA-silenced cells. Strikingly, six kallikrein (KLK)-related peptidase genes, namely KLK5, KLK6, KLK7, KLK8, KLK10, KLK12, were upregulated following silencing. Functionally, protease activity enhanced keratinocytes. Moreover, thymic stromal lymphopoietin (TSLP), epithelial-derived TH2-promoting cytokine, induced because elevated KLK activity. These results indicate deficiency leads abnormally increased may contribute TH2 immune responses inducing TSLP.
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