Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT

Farkas, Árpád; Kemény, Lajos; Szóny, Barnabás József; Bata-Csörgö, Z.; Pivarcsi, Andor; Kiss, Mária; Széll, Márta; Koreck, Andrea; Dobozy, A.

doi:10.1007/s000110050723

Cited by 43 publications

(26 citation statements)

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“…HaCaT, an immortalized cell line of human epidermal keratinocytes (Boukamp et al, 1988), which has been extensively used as an in vitro model for studies on the pathogenesis of psoriasis and evaluation of antipsoriatic drugs (Garach-Jehoshua et al, 1999;Farkas et al, 2001;Thielitz et al, 2004), was provided by the China Centre for Type Culture Collection (Wuhan, China). Hs-68, a human fibroblast cell line established from the foreskin of a normal Caucasian newborn male, was purchased from the American Type Culture Collection (Manassas, VA).…”

Section: Methodsmentioning

confidence: 99%

Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis

Tse¹,

Chen²,

Che³

et al. 2008

J Pharmacol Exp Ther

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Arsenic compounds have been traditionally used to treat a variety of ailments, including skin diseases. Our previous study identified the extract of realgar to possess potent antiproliferative action on HaCaT cells. The present study aimed at evaluating whether several inorganic arsenics found in realgar also possess similar antiproliferative properties. The results showed that arsenic trioxide, arsenic pentoxide, and arsenic iodide had significant antiproliferative action on HaCaT cells, with IC 50 values at 2.4, 16, and 6.8 M, respectively. However, these compounds only modestly inhibited the growth of Hs-68 cells, a normal human skin fibroblast cell line, with IC 50 values at 43.4, 223, and 89 M, respectively, conferring a favorable toxicity profile. In mechanistic studies, all three compounds caused DNA fragmentation as demonstrated by gel electrophoresis and the terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling method. Morphologically, nuclear condensation and DNA fragmentation were observed when the cells were exposed to arsenic compounds. Cell cycle analysis with propidium iodide (PI) staining demonstrated the appearance of sub-G 1 peak and cell arrest at the G 1 phase in the presence of these compounds. Quantitative analysis by annexin V-PI staining revealed that the arsenic-induced apoptotic event was dose-dependent. Moreover, the arsenic compounds were able to activate caspase-3 expression when examined by Western blot analysis. Our experimental data unambiguously demonstrated that induction of cellular apoptosis was mainly responsible for the observed antiproliferation brought about by the arsenic compounds on HaCaT keratinocytes, suggesting that these arsenic compounds are putative agents from which psoriasis-treating topical formulae could be developed.Arsenics are inorganic metalloids that are ubiquitously distributed throughout the Earth's crust. For centuries, some of these inorganic compounds have been used to treat a variety of ailments in many traditional medical systems. In Chinese medicine, for example, arsenic-containing minerals are primarily prescribed for the topical treatment of scabies, carbuncles, herpes zoster, enduring ulcers, psoriasis, and arthritis (Jiangsu New Medical College, 1986;Hua et al., 2003). In our previous study, realgar, a mineral commonly used in Chinese medicine for topical treatment of psoriasis and the main chemical constituent of which is As 2 S 2 , was found to be a potent antiproliferative agent on HaCaT cells (Tse et al., 2006). This promising experimental finding stimulated us to further investigate whether other arsenic compounds also possess similar antiproliferative properties. The identification of active antiproliferative arsenics and the elucidation of their action mechanism would lead to the development of topical agents for effective management of psoriasis.Affecting approximately 2% of the population worldwide, psoriasis is a common chronic inflammatory skin disease (Lebwohl, 2003;Nickoloff and Nestle, 2004). Histologically,...

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Section: Methodsmentioning

confidence: 99%

Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis

Tse¹,

Chen²,

Che³

et al. 2008

J Pharmacol Exp Ther

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“…Dithranol treatment was performed following a procedure previously described by Farkas et al (2001) with minor modifications (Tencomnao et al, 2009). In brief, cultured HaCaT cells at about 90% confluence in a 60-mm plate were washed with phosphate buffered saline (PBS) under sterile conditions and were incubated for 30 min at 37°C in a humidified atmosphere at 5% CO 2 with increasing concentrations of dithranol (0.1, 0.25 and 0.5 mg/mL) (Sigma, St. Louis, MO, USA) in DMEM containing 0.5% FBS.…”

Section: Dithranol Treatmentmentioning

confidence: 99%

“…Therefore, this particular cell line could be considered a promising tool for studying the regulation of keratinization in human cells (Boukamp et al, 1988). The HaCaT cell line was chosen for this study since it has been demonstrated to be a suitable cellular model of psoriasis according to previous reports (Farkas et al, 2001;Tencomnao et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Ronpirin¹,

Tencomnao²

2012

Genet. Mol. Res.

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ABSTRACT. Although the precise causes of psoriasis remain to be elucidated, psoriasis has been known as a disorder in which factors in the immune system, enzymes and other biochemical substances that regulate skin cell division are functionally imbalanced, thereby resulting in rapid proliferation of keratinocytes and incomplete keratinization. The expression of candidate genes such as E2A and caspase-9, which have been recognized to play a critical role in cellular proliferation/ differentiation and apoptosis, is of great interest. They may be therapeutically targeted by the antipsoriatic drug, dithranol. We examined the molecular effects of dithranol on the mRNA and protein expression levels of E2A and caspase-9 in the HaCaT keratinocyte cell line. The HaCaT cells were treated with 0-0.5 µg/mL dithranol for 30 min. After dithranol was washed out, the HaCaT cells were cultured for 2 h, and their total cellular RNA and proteins were isolated. Quantitative realtime reverse transcriptase-polymerase chain reaction and Western blot were performed to determine the mRNA and protein levels of these two genes. We found that dithranol treatment in the range of 0.25-0.5 µg/ mL slightly upregulated the mRNA expression of E2A and caspase-9 approximately 1.5-and 1.2-fold, respectively. However, undetectable Expression of E2A and caspase-9 gene in response to dithranol change and minor downregulation of the protein expression levels were observed for E2A and caspase-9, respectively. Consequently, these genes appear not to be viable therapeutic targets for dithranol.

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“…HaCaT cell line, which is a spontaneously immortalized line of human epidermal keratinocytes that exhibits normal differentiation (5) and has been extensively used as an in vitro model for the studies of psoriasis (6)(7)(8), was obtained from the China Centre for Type Culture Collection, Wuhan, Hubei Province, China. The HaCaT cells were routinely maintained in DMEM supplemented with 10% FCS, 10 μg/ml streptomycin and 10 U/ml penicillin and incubated at 37˚C in a 5% CO 2 , 95% air humidified atmosphere.…”

Section: General Cell Culturementioning

confidence: 99%

Realgar-mediated growth inhibition on HaCaT human keratinocytes is associated with induction of apoptosis

Tse

Chen²,

Che³

et al. 2009

Int J Mol Med

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Abstract. Traditional Chinese medicine has long been used to treat a variety of ailments including skin diseases. Our previous study has revealed the ethanolic extract of realgar, a common ingredient used in psoriasis treatment in Chinese medicine, to possess potent anti-proliferative action on cultured HaCaT cells of human keratinocyte origin. In the present study, the mechanisms of action of the observed growth inhibitory action of realgar were investigated. Several bioassay methods were employed to elucidate whether cellular apoptosis is involved in the realgar-induced growth inhibition of the skin cells. Morphologically, nuclear condensation and DNA fragmentation were observed when HaCaT cells were exposed to the realgar extract. DNA fragmentation induced by the treatment of realgar was also evident as detected by gel electrophoresis and the TUNEL method. Cell cycle analysis by propidium iodide (PI) staining demonstrated the appearance of sub-G1 peak and cell cycle arrest at the G1 phase upon realgar treatment. Quantitative analysis by annexin V-PI staining revealed that the realgar-induced apoptotic event was dose-dependent. Furthermore, realgar was able to activate caspase-3 expression when examined by Western blot analysis. Our experimental data unambiguously confirm that induction of cellular apoptosis is mainly responsible for the observed growth inhibition brought about by realgar on the HaCaT keratinocytes, and this finding helps place the traditional use of this mineral for psoriasis treatment on a scientific footing.

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Dithranol upregulates IL-10 receptors on the cultured human keratinocyte cell line HaCaT

Abstract: 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.

Cited by 43 publications

References 50 publications

Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis

Arsenic Trioxide, Arsenic Pentoxide, and Arsenic Iodide Inhibit Human Keratinocyte Proliferation through the Induction of Apoptosis

Effects of the antipsoriatic drug dithranol on E2A and caspase-9 gene expression in vitro

Realgar-mediated growth inhibition on HaCaT human keratinocytes is associated with induction of apoptosis

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