Molecular mechanisms of tazarotene action in psoriasis.
Psoriasis is a chronic immune-mediated disease that is characterized by the hyperproliferation and abnormal differentiation of keratinocytes and by inflammation. The epidermal changes associated with psoriasis may be due to the infiltration of inflammatory T lymphocytes and the release of cytokines in response to antigenic stimulation. Tazarotene is a retinoic acid receptor-specific retinoid with demonstrated efficacy in the topical treatment of psoriasis. Tazarotene down-regulates markers of keratinocyte differentiation, keratinocyte proliferation, and inflammation. The drug also up-regulates three novel genes TIG-1 (tazarotene-induced gene-1), TIG-2, and TIG-3, which may mediate an antiproliferative effect. The effect of tazarotene on these markers is probably a direct effect on gene expression rather than an indirect effect associated with disease improvement.
Duvic
M
M
Department of Dermatology, University of Texas Medical School, Houston 77030, USA.
Nagpal
S
S
Asano
A T
AT
Chandraratna
R A
RA
D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D009539:Nicotinic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D012176:Retinoids / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects
D003879:Dermatologic Agents; D009539:Nicotinic Acids; D011355:Prodrugs; D012176:Retinoids; C086827:tazarotene