Effects of acitretin on proliferative inhibition and RANTES production of HaCaT cells.
Acitretin is one of the first line drugs to treat psoriasis, though the mechanisms are not fully clear. It has been reported that psoriatic keratinocytes secreted high level of RANTES, which can induce chemotaxis and activation of T cells, thus may play an important role in the pathogenesis of psoriasis. However, the effect of acitretin on RANTES production of human keratinocytes and its possible signaling are unclear. We observed a significant inhibition of acitretin on proliferation of human keratinocytes cell line (HaCaT cells) by MTT assay. The inhibition rate of HaCaT cells growth increased gradually from 13.70 to 67.73% with acitretin concentration rising from 0.01 to 50 micromol/L. In addition, RANTES expression detected in supernatant of HaCaT cells stimulated with TNF-alpha and IFN-gamma reduced 25, 18 and 12%, respectively, when cultured with 0.1, 1 and 5 micromol/L acitretin. Furthermore, 1 micromol/L acitretin significantly decreased RANTES mRNA level. Finally, acitretin decreased the expressions of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa B (NFkappaB) in nuclei of HaCaT cells stimulated with TNF-alpha and IFN-gamma, which were determined by immunocytochemistry and western blot. It suggests that acitretin can inhibit proliferation and RANTES production of human epidermal keratinocytes, and the latter may be related to the inhibition of nuclear translocations of STAT1 and NFkappaB.
Zhang
Min
M
Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China.
Zhu
Ling
L
Feng
Yun
Y
Yang
Yunxia
Y
Liu
Liao
L
Ran
Yuping
Y
D017255:Acitretin / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D018946:Chemokine CCL5 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007641:Keratolytic Agents / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018946:Chemokine CCL5; D007641:Keratolytic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D017255:Acitretin