DZ2002 improves psoriasis-like lesions of guinea pig via inhibiting secretion of chemokines in keratinocytes / 中国药理学通报

ABSTRACT

Aim To explore the therapeutic effect of DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase inhibitor, on psoriasis-like skin lesions of guinea pig and its mechanism. Methods The guinea pig model of psoriasis was established with 50 g • L-1 propranolol hydrochloride liniment. The pathological changes of the skin were determined by hematoxylin and eosin (HE). Then the Baker score and epidermal thickness were measured based on HE. The infiltration of neutrophils was marked by immunohistochemical staining. The expression of chemokines in TNF-a/IFN-7-treated HaCa T cells in the present of DZ2002 or not were determined by real-time polymerase chain reaction (RT-PCR), and the production of chemokines from HaCa T cells were quantified by ELISA and Luminex x-MAP technology. In the same condition, supernatants were used to test the Chemotaxis effect on Jurkat and THP1 cells via Chemotaxis assays. Results Pathological features such as acanthosis, inflammatory cell infiltration, Munro microabscess, hyperkeratosis and parakeratasis appeared in the psoriasis-like skin lesions of guinea pigs. The Baker score and epidermal thickness of psoriasis-like guinea pig ear both increased significantly. Compared with vehicle group, DZ2002 cream not only significantly improved the pathological manifestations of guinea pig ear skin, but also reduced the skin Baker score and epidermal thickness. DZ2002 significantly down-regulated the expression of chemokines including IL-8 and CXCL9 in TNF-0/IFN-7treated HaCaT cells, and inhibited the Chemotaxis of THP1 and Jurkat cells. Conclusions DZ2002 cream can significantly improve the psoriasis symptoms in guinea pig model of psoriasis via inhibiting the secretion of chemokines by keratinocytes and reducing the infiltration of inflammatory cells.