THREE DIMENSIONAL (3D) RECONSTRUCTED PSORIATIC TISSUE MODEL.
Psoriasis is a chronic skin disease that affects about 2% of the global population. Availability of well characterized in vitro psoriatic tissue model will enhance our understanding of the disease and the development of therapeutic strategies. In this study, an in vitro three-dimensional psoriatic-like tissue model was reconstructed, culture conditions were optimized, and the model was characterized using H & E staining (morphology), immunohistochemistry (proliferation of basal cells as demonstrated by the Ki67 staining profile, psoriasin expression), RT-PCR (gene expression levels), and ELISA assays (cytokine analysis). Results showed that the reconstructed psoriatic 3-D tissue model has phenotypic and architectural similarity to the in vivo counterpart in that the tissue model showed over expression of biomarkers associated with psoriasis including human beta defensin-2 (HBD-2), psoriasin, and CXCR2. Similar to the in vivo situation, cytokine analysis of culture supernatants from the psoriatic-like tissue model showed increased release of IL-6 (7 fold), IL-8 (5.5 fold), and GRO-α (3.8 fold) by the psoriatic tissue model when compared to normal reconstructed epidermal tissues. Treatment of the psoriatic-like tissue with IL-4 or calcipotriol showed a dose dependent decrease in HBD-2 gene expression and IL-6 release (3.0-4.3 fold). In conclusion, the psoriatic tissue model mimics the in vivo counterpart in terms of tissue morphology, tissue structure, gene expression (CXCR2, beta defensin, and psoriasin), and cytokine release (IL-6, IL-8, GRO-a). The model can serve as a valuable tool to study the biology of psoriasis and for preclinical assessment of toxicity and proinflammatory effects of therapeutic candidates.
Calgranulin A, Calgranulin B, Calgranulin C, CXCR2, Cystatin A, Cytokeratin 10, cytokeratin 17, Cytokeratin-16, Effector proteins, Elafin, ENA-78, GCP-2, GROα, HBD-2, Human beta defensin-2 (HBD-2), Human beta defensin-3, IL-6, IL-8, Interleukin 6, Interleukin 8, Involcurin, IP-9, Lactotransferin, LL-37, LPS binding protein, MIP-3a, Psoriasin, Psoriasis, Psoriatic tissue models (PTM), RIGI, Secretory Leukocyte Peptidase Inhibitor, TLR2, TLR3, TLR5, TLR6, TLR9, Transglutaminase, α-defensin-3
Calcipotriol hydrate, IL-4
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