Ameliorative effects of a fusion protein dual targeting interleukin 17A and tumor necrosis factor α on imiquimod-induced psoriasis in mice

• Published in: Biomedicine & pharmacotherapy Vol. 108; pp. 1425 - 1434
• Main Authors: Liu, Zhihang, Liu, Han, Xu, Pengfei, Yin, Qi, Wang, Yaoqun, Opoku, Yeboah Kwaku, Yang, Jiarui, Song, Liying, Sun, Xu, Zhang, Teng, Yu, Dan, Wang, Xiangxiang, Ren, Guiping, Li, Deshan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2018
• Subjects: Animals; Antigens, Ly - genetics; Caspase 14 - genetics; Dual targeting fusion protein; Etanercept - therapeutic use; Female; Imiquimod - toxicity; Imiquimod-induced psoriasis; Inflammation; Interleukin 17A; Interleukin-17 - antagonists & inhibitors; Intermediate Filament Proteins - genetics; Keratin-16 - analysis; Keratin-17 - analysis; Keratin-6 - analysis; Mice; Mice, Inbred BALB C; Psoriasis - chemically induced; Psoriasis - drug therapy; Tumor necrosis factor α; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Inflammation; Imiquimod-induced psoriasis; Dual targeting fusion protein; Tumor necrosis factor α; Interleukin 17A
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.178

[Display omitted] •DTF could target IL-17 A and TNF-α simultaneously.•DTF treatment significantly attenuated IMQ-induced psoriasis in mice.•DTF was more potent than etanercept in ameliorating IMQ-induced psoriasis.•DTF reduced the expression of keratins in psoriasis-like skin in mice.•DTF enhanced the expression of filaggrin and caspase 14 in mice. In recent decades, biological agents such as tumor necrosis factor-α (TNF-α) inhibitors, have revolutionized the treatment of psoriasis. However, inhibition of a single cytokine may not achieve satisfactory therapeutic results. It is against this background that this research was undertaken to investigate the anti-psoriatic effect of a novel fusion protein (DTF) dual targeting TNF-α and interleukin-17 A (IL-17 A). Imiquimod (IMQ) was topically applied to the skin of mice to develop psoriasis-like skin and treated with etanercept or different doses of DTF. Results showed that DTF treatment (1 mg/kg, 3 mg/kg, 5 mg/kg) significantly attenuated IMQ-induced typical psoriasis-like inflammation, severity score, and epidermis thickening in a dose-dependent manner, and was again more efficient than etanercept (3 mg/kg) in alleviating all these parameters at the same dose. Furthermore, DTF was more potent than etanercept in suppressing the expression of inflammatory factors (IL-17 A, IL-6, IL-1β, IL-23, IL-22 and IL-12) in the serum, spleen and psoriasis-like skin compared with etanercept at the same dose. In addition, DTF was more efficient than etanercept in reducing the expression of keratins, decreasing the mRNA expression of Ly-6 G and Ly-6C, and enhancing the expression of filaggrin and caspase 14 in IMQ-induced psoriasis-like skin. We conclude that DTF alleviates IMQ–induced psoriasis by attenuating inflammatory cascades, reducing keratinocytes proliferation and improving epidermal barrier function through suppressing TNF-α and IL-17 A signal pathways. These data suggest that DTF has potential to be a novel therapeutic candidate for psoriasis.