Topical application of a new monoclonal antibody against fibroblast growth factor 10 (FGF 10) mitigates propranolol-induced psoriasis-like lesions in guinea pigs

N. YAO; J.-X. XIA; X.-M. LIU; N. WANG; X.-G. MMI; Y.-F. WANG; L.-L. GUAN; J. YANG; Y.-Y. DONG; F.-W. WANG; H.-Y. LI; X.-K. LI
April 2014
European Review for Medical & Pharmacological Sciences;Apr2014, Vol. 18 Issue 7, p1085
Academic Journal
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)-2,5diphenyltetrazolium 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 antiFGF10. The pathologic changes and the degrees of inflammation in the auricular areas of individual animals were examined histologically. RESULTS: Characterization revealed that antiFGF10 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 antiFGF10 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 psoriasislike 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 antiFGF10 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.


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