Abstract: We cultured human hair follicle-derived keratinocytes (FDKs) from plucked hairs. To gain insight into gene expression signatures that can distinguish atopic dermatitis from non-atopic controls without skin biopsies, we undertook a comparative study of gene expression in FDKs from adult donors with atopic dermatitis and non-atopic donors. FDK primary cultures (atopic dermatitis, n = 11; non-atopic controls, n = 7) before and after interferon gamma (IFN-γ) treatment were used for microarray analysis and quantitative RT-PCR. Comparison of FDKs from atopic and non-atopic donors indicated that the former showed activated pathways with innate immunity and decreased pathways of cell growth, as indicated by increased NLRP2 expression and decreased DKK1 expression, respectively. Treatment with IFN-γ induced the enhanced expression of IL32, IL1B, IL8, and CXCL1 in the cells from atopic donors compared to that in cells from non-atopic donors at 24 h after treatment. IL1B expression in FDKs after IFN-γ treatment correlated with IL32 expression. We hypothesized that overexpression of IL32 in hair follicle keratinocytes of patients with atopic dermatitis would lead to the excessive production of pro-IL1β and that the activation of IL1β from pro-IL1β by inflammasome complex, in which NLRP2 protein might be involved, would be augmented. This is the first report to show enhanced induction of cytokine/chemokine genes by IFN-γ in atopic dermatitis using cultured FDKs.
Keywords: gene profiling; hair follicle-derived keratinocytes; atopic dermatitis; IL32
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Yoshikawa, Y.; Sasahara, Y.; Takeuchi, K.; Tsujimoto, Y.; Hashida-Okado, T.; Kitano, Y.; Hashimoto-Tamaoki, T. Transcriptional Analysis of Hair Follicle-Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN-γ. Int. J. Mol. Sci. 2013, 14, 3215-3227.
Yoshikawa Y, Sasahara Y, Takeuchi K, Tsujimoto Y, Hashida-Okado T, Kitano Y, Hashimoto-Tamaoki T. Transcriptional Analysis of Hair Follicle-Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN-γ. International Journal of Molecular Sciences. 2013; 14(2):3215-3227.
Yoshikawa, Yoshie; Sasahara, Yusuke; Takeuchi, Katsuyuki; Tsujimoto, Yoshimasa; Hashida-Okado, Takashi; Kitano, Yukio; Hashimoto-Tamaoki, Tomoko. 2013. "Transcriptional Analysis of Hair Follicle-Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN-γ." Int. J. Mol. Sci. 14, no. 2: 3215-3227.