Abstract |
Recent studies have demonstrated that orally administered thiazolidinedione ligands of the peroxisome proliferator-activated receptor-gamma can ameliorate clinical features of psoriasis in humans. Thiazolidinediones also inhibit the proliferation of psoriatic keratinocytes in monolayer and organ culture, and at least one of these agents ( troglitazone) inhibits epidermal hyperplasia of human psoriatic skin transplanted to severe-combined immunodeficient (SCID) mice. In the present study, we show that a novel, synthetic, thiazoladinedione derivative, BP-1107 ({2-[4-(2,4-dioxo-thiazolidin-5-ylmethyl)-phenoxy]-ethyl}-methyl- amide), is capable of inhibiting psoriatic hyperplasia in the SCID mouse transplant model after topical application. Like other thiazolidinediones, BP-1107 inhibits proliferation of rapidly growing keratinocytes in monolayer culture, but compared with these agents, the effective dose of BP-1107 needed to suppress keratinocyte proliferation is much lower. Concentrations of BP-1107 that effectively inhibit keratinocyte function have no detrimental effect on dermal fibroblasts. These data suggest that effective topical antipsoriatic therapy may be provided with this agent.
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Authors | Narasimharao Bhagavathula, Kamalakar C Nerusu, Mahendranath Reddy, Charles N Ellis, Amar Chittiboyina, Mitchell Avery, Harrihar A Pershadsingh, Theodore W Kurtz, James Varani |
Journal | The Journal of pharmacology and experimental therapeutics
(J Pharmacol Exp Ther)
Vol. 315
Issue 3
Pg. 996-1004
(Dec 2005)
ISSN: 0022-3565 [Print] United States |
PMID | 16109743
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- 5-adamantylpentanoic acid (2-(4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxy)ethyl)(methyl)amide
- Thiazolidinediones
- Adamantane
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Topics |
- Adamantane
(analogs & derivatives, chemistry, therapeutic use)
- Administration, Topical
- Animals
- Epidermis
(drug effects, metabolism, pathology)
- Humans
- Hyperplasia
(drug therapy, metabolism, pathology)
- Mice
- Mice, SCID
- Molecular Structure
- Psoriasis
(drug therapy, genetics, metabolism)
- Skin Transplantation
- Thiazolidinediones
(chemistry, metabolism, therapeutic use)
- Time Factors
- Transplantation, Heterologous
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