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

作者：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^*

来源：Biomedicine & Pharmacotherapy, 2018, 108: 1425-1434.

DOI：10.1016/j.biopha.2018.09.178

• Imiquimod-induced psoriasis
• Inflammation
• Dual targeting fusion protein
• Interleukin 17A
• Tumor necrosis factor alpha

In recent decades, biological agents such as tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-1 beta, 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 alpha and IL-17 A signal pathways. These data suggest that DTF has potential to be a novel therapeutic candidate for psoriasis.

• 出版日期2018-12
• 单位东北农业大学