Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT.
OBJECTIVE
Dithranol is highly effective in the treatment of psoriasis, however its mode of action is still not well known. Since interleukin-8 and interleukin-10 are involved in the pathogenesis of psoriasis, the aim of our study was to investigate the effect of dithranol on interleukin-8, interleukin-10 mRNA production and interleukin-10 receptor expression of the HaCaT keratinocyte cell line which is commonly used in experiments examining the effects of therapeutic drugs on keratinocytes.


METHODS
Cultured HaCaT cells were treated with 0.1-0.5 microg/ml dithranol for 30 minutes. After 2 and 4 h total cellular RNA isolated from HaCaT cells was reverse transcribed (RT) to cDNA which was subjected to polymerase chain reaction (PCR) with specific primer pairs for interleukin-8, interleukin-10 and interleukin-10 receptor. For immunohistochemistry cultured HaCaT cells were stained with a monoclonal antibody against the human interleukin-10 receptor.


RESULTS
Our results showed that dithranol treatment did not change the highly elevated level of interleukin-8 mRNA of HaCaT cells. Interleukin-10 mRNA signal with RT-PCR could not be detected in HaCaT cells. Depending on the concentration dithranol increased the mRNA production of interleukin-10 receptors in HaCaT cells. This dithranol induced dose dependent upregulation of IL-10 receptors in HaCaT cells was also observed on the protein level using immunohistochemistry.


CONCLUSIONS
Since the interleukin-10 receptor expression of keratinocytes in psoriatic lesional skin is downregulated, the dithranol induced upregulation of the receptor in our model system might help to reveal the therapeutic action of the drug.
Department of Dermatology, Faculty of General Medicine, University of Szeged, Hungary. farkas@derma.szote.u-szeged.hu
A
A
Farkas
L
L
Kemény
B J
BJ
Szöny
Z
Z
Bata-Csörgö
A
A
Pivarcsi
M
M
Kiss
M
M
Széll
A
A
Koreck
A
A
Dobozy
D000199:Actins / Q000235:genetics; D000287:Administration, Topical; D000875:Anthralin / Q000008:administration & dosage / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D053701:Receptors, Interleukin-10; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D000875:Anthralin