Objectives: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes. Fibroblast growth factor 10 (FGF10) acts as a growth factor for keratinocyte proliferation. The aim of this study is to investigate whether FGF10 blockage, a new monoclonal antibody against FGF10 we generated, could mitigate topical propranolol-induced psoriasis-like lesions in guinea pigs.
Materials and methods: The monoclonal anti-FGF10 was generated by a routine method and purified by affinity chromatography. The effect of FGF10 and anti-FGF10 on human keratinocyte HaCaT cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The back of the ears of individual guinea pigs was topically exposed to 5% propranolol emulsion to induce psoriasis-like lesions and randomly treated topically with phosphate buffered saline (PBS), hydrocortisone butyrate, or different doses of anti-FGF10. The pathologic changes and the degrees of inflammation in the auricular areas of individual animals were examined histologically.
Results: Characterization revealed that anti-FGF10 had a purity of 90% and a titer of 1:12800. We found that FGF10 stimulated HaCaT cell proliferation while treatment with different doses of anti-FGF10 inhibited FGF10-induced cell proliferation in a dose-dependent manner (100, 200 ng/ml, p < 0.05 vs. control; 400, 800, 1600 ng/ml, p < 0.01 vs. control). Compared to PBS-treated psoriatic animals, treatment with anti-FGF10, like hydrocortisone butyrate, greatly inhibited the severity of psoriasis-like lesions by reducing the Baker's scores, the thickness of epidermis, and the numbers of monocyte infiltrates in the dermis of animals.
Conclusions: The newly generated anti-FGF10 monoclonal antibody inhibited the proliferation of human keratinocytes in vitro and mitigated inflammation and pathogenic changes in propranolol-induced psoriasis-like lesions in animals. Therefore, these findings may provide a proof of principle that blockage of FGF-10 may inhibit psoriasis-related inflammation.