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Inhibition of tumour necrosis factor‐α secretion from EpiDerm TM tissues by a novel small molecule, UTL‐5d
Author(s) -
Shaw J.,
Liu C.,
Martin R.,
Chen B.,
Holtz R.,
Huang WH.,
Lee AR.
Publication year - 2007
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2007.08025.x
Subject(s) - psoriasis , lotion , tumor necrosis factor alpha , epidermis (zoology) , secretion , necrosis , cell , medicine , cancer research , in vitro , pharmacology , chemistry , immunology , pathology , biochemistry , anatomy
Summary Background UTL‐5d [ N ‐(4‐chlorophenyl)‐3‐carboxyamidyl‐5‐methylisoxazole] is a small‐molecule tumour necrosis factor (TNF)‐α modulator being investigated for its potential in several immune‐mediated diseases, including psoriasis. Objectives We aimed to determine whether UTL‐5d represents a potential antipsoriasis agent. Methods Firstly, a keratinocyte cell‐based study was used to study the inhibition of TNF‐α and gene suppression by UTL‐5d in vitro . Secondly, a multilayered human epidermis tissue model, consisting of normal human‐derived epidermal keratinocytes, was used to study the dose‐dependent reduction of TNF‐α by UTL‐5d as well as the feasibility of using UTL‐5d in a lotion formulation. Results The cell‐based study showed that UTL‐5d significantly reduced TNF‐α secretion from keratinocytes (68% reduction at 17 μg mL −1 ) and suppressed JAK3 and MAP3K2 genes by 70% and 40%, respectively. In the human epidermis tissue model, reduction of TNF‐α by UTL‐5d appeared to be dose dependent (8·35–33·4 μg mL −1 ); UTL‐5d also reduced cell death induced by ultraviolet (UV) B. Tissues treated by UTL‐5d in a preliminary lotion formulation showed significant reduction of TNF‐α induced by UVB. Conclusions Our results indicate that UTL‐5d may be worthy of further investigation for its potential as a topical agent for psoriasis.