| DOI: 10.29090/psa.2026.02.25.8186 | Pharm Sci Asia 2026; 53(2), 166-178 |
Utilization of HaCaT-derived psoriatic skin models in assessing the therapeutic potential of pharmacological agentsIntira Pathtubtim1,4, Thanchanok Muangman1,*, Sasithon Temisak 2, Celine Viennet 3, Jarupa Viyoch 4,*
1 Expert Centre of Innovative Health Food, Thailand Institute of Scientific and Technological Research (TISTR), Techno Polis, Klong Luang, Pathum Thani 12120, Thailand
2
National Institute of Metrology (NIMT) PathumThani 12120
3
UMR 1098 RIGHT INSERM EFS FC, DImaCell Imaging Resource Center, University of Marie&Louis Pasteur, Besancon 25000, France
4
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry (PERCH-CIC), Naresuan University, Phitsanulok 65000, Thailand
Psoriasis is a prototypic example of an immune-mediated skin disorder, characterized by abnormal keratinocyte differentiation, barrier dysfunction, and excessive production of pro-inflammatory cytokines. Here, a psoriasis-like human reconstructed epidermis (RHE-Pso) model was established by cytokine treatment of HaCaT keratinocytes with a cytokine mixture (IL-1α, TNFα, IFN-γ). This model manifested a psoriasis-like phenotype, characterized by reduced TER values, altered epidermal histomorphology, as well as a reduction in Filaggrin (FLG) expression at the protein as well as mRNA levels, accompanied by a marked enhancement in the release of cytokines like IL-1α, IL-8, TNFα, and IFN-γ. Later, this RHE-Pso model has been employed to assess various pharmacologic as well as natural agents. Clobetasol propionate emerged as one of the most effective agents in reclaiming TER values, increasing FLG mRNA expression (3.40 ± 0.37-fold of control), as well as curtailing the release of cytokines. Retinoic acid increased FLG mRNA (2.85 ± 0.35-fold of control) as well as moderately inhibited cytokine secretion, whereas calcipotriol partially relieved barrier restoration. A comparative analysis of natural agents revealed that quercetin increased FLG mRNA as well as inhibited TNFα & IFN-γ levels, whereas resveratrol relieved TER values as well as specifically inhibited cytokine release. Conversely, curcumin exhibited minimal activity. Taken together, this data propose that the HaCaT-derived RHE-Pso model can act as a promsing pre-clinical in vitro model in defining anti-psoriasis drug leads as well as natural bioactive agents.
Keyword:
HaCaT; Psoriasis-like 3D skin model (RHE-Pso); Pharmacological agents.
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