4.4 Article

HaCaT Keratinocytes and Primary Epidermal Keratinocytes Have Different Transcriptional Profiles of Cornified Envelope-Associated Genes to T Helper Cell Cytokines

Journal

BIOMOLECULES & THERAPEUTICS
Volume 20, Issue 2, Pages 171-176

Publisher

KOREAN SOC APPLIED PHARMACOLOGY
DOI: 10.4062/biomolther.2012.20.2.171

Keywords

HaCaT Keratinocytes; Cornified envelope associated genes; HBD2; IFN gamma; IL-4; IL-17A

Funding

  1. Ministry of Health & Welfare, Republic of Korea [A103017]
  2. Korea Health Promotion Institute [A103017] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as IFN gamma, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human beta 2-defensin (HBD2) in response to IFN gamma, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. IFN gamma also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to IFN gamma, IL-4 or IL-17A.

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