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  • Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.

Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.

Biomedicines (2022-08-27)
Ben Jin, Yongfeng Zhang, Haiyan D Miller, Ling He, Dongxia Ge, Alun R Wang, Zongbing You
ABSTRACT

Patients with psoriasis tend to develop skin cancer, and the hyperproliferation of the epidermis is a histopathological hallmark of both psoriasis and cutaneous squamous cell carcinoma (SCC), indicating that they may share pathogenic mechanisms. Interleukin-17 (IL17) stimulates the proliferation of the epidermis, leading to psoriasis. Overexpression of Polo-like kinase 4 (PLK4), which controls centriole duplication, has been identified in SCC, which also shows the hyperproliferation of keratinocytes. To investigate the cooperation between IL17 signaling and centriole duplication in epidermal proliferation, we established psoriasis and skin papilloma models in wild type (WT), IL17 receptor A (T779A) knockin (Il17ra(T779A)-KI), and IL17 receptor C knockout (Il17rc-KO) mouse strains. Bioinformatics, Western blot, immunohistochemical staining, colony formation, and real-time PCR were used to determine the effect of IL17 signaling and centrinone on epithelial proliferation. In the psoriasis model, compared to WT and Il17ra(T779A)-KI, Il17rc-KO dramatically suppressed epidermal thickening. The proliferation of keratinocytes significantly decreased in this order from WT to Il17ra(T779A)-KI and Il17rc-KO mice. In the skin papilloma model, Il17ra(T779A)-KI significantly decreased tumor burden compared to the WT, while Il17rc-KO abolished papilloma development. However, centrinone, a selective inhibitor of PLK4, did not affect skin lesion formation in either model. Our data demonstrated that Il17ra(T779A)-KI and Il17rc-KO prevent the development of psoriasis and tumorigenesis in the skin, while the topical administration of centrinone does not have any effect.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PMA, for use in molecular biology applications, ≥99% (HPLC)
Sigma-Aldrich
Protease Inhibitor Cocktail, for use in purification of Histidine-tagged proteins, DMSO solution
Sigma-Aldrich
Anti-PLK4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-GAPDH Antibody, from chicken, purified by affinity chromatography