Apoptosis in Established and Healing Psoriasis

Laporte, Marianne; Galand, Paul; Fokan, Dominique; Graef, Chantal De; Heenen, Michel

doi:10.1159/000018394

Cited by 94 publications

(90 citation statements)

References 11 publications

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“…So far, there has been little research on Bcl-2 expression in psoriatic epidermis. Most authors have concentrated on apoptosis of keratynocytes, but not lymphocytes [7,31]. Avramidis et al [32] found significant reduction in Bcl-2 and induction of apoptosis in endothelial cells of patients with psoriasis during etanercept treatment.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CD40, its ligand CD40L and Bcl-2 in psoriatic patients

Myśliwiec

Flisiak

Baran

et al. 2012

Folia Histochem Cytobiol.

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Psoriasis is a chronic, recurrent, inflammatory disease. Recent investigations indicate an autoimmune pathogenesis of the disease. Apoptosis plays an important role in the regulation of immune mechanisms in many autoimmune diseases. Although CD40, CD40L, and Bcl-2 have already been studied in psoriatic skin lesions, little is known about their circulating forms. The aim of the present study was to evaluate the serum concentrations of Bcl-2, soluble CD40 and CD40L in psoriatic patients. The study was performed using ELISA kits in 39 psoriatic patients before treatment and after two weeks of topical ointment. Data was analyzed with respect to severity of psoriasis, duration of the disease, and coexisting psoriatic arthritis. Our results revealed that serum concentrations of soluble CD40 and CD40L before and after treatment were significantly higher (p < 0.01 and p < 0.001) in patients with psoriasis compared to the control group. Topical treatment of psoriatic lesions with dithranol ointment failed to decrease serum of CD40 and CD40L, which has not been described until now. There was no significant difference in serum Bcl-2 concentration between the compared groups. We did not find significant differences in serum concentrations of Bcl-2, CD40 or CD40L between patients with mild or severe psoriasis, nor any correlation between disease duration and the presence of psoriatic arthritis symptoms. Our data indicates upregulation of the CD40/CD40L system in psoriatic patients despite topical treatment and suggests their possible role in the pathogenesis of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Evaluation of CD40, its ligand CD40L and Bcl-2 in psoriatic patients

Myśliwiec

Flisiak

Baran

et al. 2012

Folia Histochem Cytobiol.

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“…On the contrary, defects in epidermal apoptosis will result in hyperproliferation of keratinocytes, the underlying pathogenesis of psoriasis (Kawashima et al, 2004). Indeed, the apoptotic index of the basal cell layer in psoriatic epidermis (0.035%) is significantly lower than that of healthy skin (0.12%) (Laporte et al, 2000). Agents that induce keratinocyte apoptosis could therefore be useful in the treatment of psoriasis.…”

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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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“…The TUNEL method by TEM (TUNEL/TEM) was developed for retrospective studies using archival epoxyresin-embedded materials and enables the morphological discrimination of apoptotic cells among many cell types including necrotic or mitotic cells based on ultrastructural characteristics (Inoki et al 1997;Hayashi et al 1998;Otsuki 2000Otsuki ,2004. To date, several studies of psoriasis have shown that almost all proliferative keratinocytes are TUNEL positive, although psoriasis is a hyperproliferative disease (Laporte et al 2000). Our previous study of psoriasis by TUNEL/TEM (Kawashima et al 2004) clearly demonstrated that immunogold particles indicating the presence of free 39-OH DNA ends are localized on the nuclear euchromatin of cells in the S phase and, therefore, may actually label the site of physiological nicking yielded during DNA replication.…”

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confidence: 99%

Method of Specific Detection of Apoptosis Using Formamide-induced DNA Denaturation Assay

Ito

Shibata

Kusakabe

et al. 2006

J Histochem Cytochem.

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S U M M A R Y We compared the reliability between apoptosis detection methods, namely, the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method and formamide-induced DNA denaturation assay using a monoclonal antibody (MAb) to single-stranded DNA (ssDNA) (formamide-MAb assay). Reaction targets in these methods are different: the TUNEL method recognizes free 39-OH DNA ends, whereas the formamide-MAb assay detects ssDNA itself (25-30 bp). We found that the formamideMAb assay immunohistochemically detected apoptotic cells, whereas the TUNEL method detected apoptotic cells as well as mitotic and necrotic cells. The TUNEL method recognized not only 39-OH DNA ends cleaved by DNase during apoptosis but also constitutive physiological nicking that occurs in DNA duplication and histone posttranslational modifications during mitosis and random DNA breaks during necrotic execution. By electron microscopy, the mean labeling density (the number of 39-OH DNA ends/nuclear area) obtained by the TUNEL method was determined to be consistently higher than that (the number of ssDNAs/ nuclear area) obtained by the formamide-MAb assay. On the basis of these findings, we conclude that the formamide-MAb assay was more specific than the TUNEL method for the detection of apoptotic cells using electron microscopy; however, the labeling intensity of the formamide-MAb assay was slightly weaker than that of the TUNEL method. (J Histochem Cytochem 54:683-692, 2006)

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Apoptosis in Established and Healing Psoriasis

Cited by 94 publications

References 11 publications

Evaluation of CD40, its ligand CD40L and Bcl-2 in psoriatic patients

Evaluation of CD40, its ligand CD40L and Bcl-2 in psoriatic patients

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

Method of Specific Detection of Apoptosis Using Formamide-induced DNA Denaturation Assay

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