Immortalized Human Epidermal Keratinocytes

HDAC3 Plays a Critical Role in Keratinocyte Proliferation under Inflammatory Cytokine Stimulation

Psoriasis is known to be mediated by keratinocyte hyperproliferation and immune activation. As HDAC3 is involved in immune regulation and inflammation responses, it is hypothesized that HDAC3 may play a role in psoriasis development. Zeng's team sought to determine HDAC3 expression and contribution towards psoriasis disease models.

Since HDAC3 seemed to contribute to psoriasis phenotype, they tested the functionality of HDAC3 in immortalized human epidermal keratinocytes (HaCaT). CCK8 assays confirmed RGFP966 <10 µM was not cytotoxic to cells (Fig. 1A); they chose 5 µM as their working dose after verifying inhibition of HDAC3 (Figs. 1B-C). Models of psoriasis were created by stimulation of M1 (IL-1α + IL-17A + TNF-α) and M2 (M1 + IL-6) cytokines. Both models showed psoriasis-like morphology and expression of disease-related genes (K16, K17, S100A7, TNF-α, PI3, Ki-67), which was more profound in the M2 model (Fig. 1D-E). Additionally, M2 stimulated cells had increased proliferation that was significantly decreased after treatment with RGFP966 (Fig. 1F-G). These results highlight that HDAC3 contributes to keratinocyte hyperproliferation during psoriatic inflammation and HDAC3 inhibition rescues this disease phenotype.