MAP17 is associated with the T-helper cell cytokine-induced down-regulation of filaggrin transcription in human keratinocytes

Abstract

In the meta-analysis of public microarray databases for different skin diseases, we revealed seven commonly up-regulated genes, DSG3, KRT6, MAP17, PLSCR1, RPM2, SOD2 and SPRR2B. We postulated that the genes selected from the meta-analysis may be potentially associated with the abnormal keratinocyte differentiation. To demonstrate this postulation, we alternatively evaluated whether the genes of interest in the meta-analysis can be regulated by T-helper (Th) cell cytokines in normal human epidermal keratinocytes (NHEK). We found that MAP17 was significantly up-regulated in response to interferon-gamma, interleukin 4 (IL-4), IL-6, IL-17A or IL-22 in NHEK. Interestingly, MAP17 was originally reported to interact with PDZK1; in turn, the PDZK1 gene is localized within the atopic dermatitis-linked region on human chromosome 1q21. In an attempt to evaluate whether MAP17 regulates the expression of cornified envelope-associated genes at the 1q21 locus, such as filaggrin, loricrin and involucrin, we found that the over-expression of MAP17 in HaCaT keratinocytes significantly decreased the expression of filaggrin. Taken together, the Th cell cytokine-induced up-regulation of MAP17 expression may be linked to the down-regulation of filaggrin in NHEK, which may be associated with the abnormal epidermal differentiation observed in the dermatological diseases.