Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

Borská, Lenka; Andrýs, Ctirad; Krejsek, Jan; Hamáková, Květoslava; Kremláček, Jan; Palička, Vladimír; Ranna, D.; Fiala, Zdeněk

doi:10.1111/j.1365-4632.2009.04258.x

Cited by 18 publications

(12 citation statements)

References 30 publications

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“…Wykazano również, że promieniowanie UVB oraz metotreksat indukują apoptozę limfocytów T w obrębie zmian łuszczycowych [45,46]. Odnotowano także znaczne nasilenie ekspresji FasL po naświetlaniach UVB [28] oraz w trakcie leczenia metodą Goeckermana [47]. Leczenie cyklosporyną A w badaniach in vitro zmniejsza ekspresję CD40L na limfocytach T [23].…”

Section: Apoptoza W łUszczycyunclassified

Selected aspects of apoptosis in psoriasis

Myśliwiec¹,

Baran²,

Flisiak³

2017

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StreSzczenIeApoptoza jest procesem fizjologicznej, programowanej śmierci komó-rek, która w odróżnieniu od nekrozy nie powoduje stanu zapalnego. Ma podstawowe znaczenie dla funkcjonowania różnych tkanek i narządów. Równowaga pomiędzy proliferacją a apoptozą keratynocytów jest istotna dla prawidłowej homeostazy naskórka. W schorzeniach skóry może dochodzić do pobudzenia apoptozy, co prowadzi zazwyczaj do chorób o ostrym przebiegu, lub jej zahamowania, co skutkuje częściej rozwojem chorób przewlekłych. Łuszczyca jest przewlekłą chorobą zapalną charakteryzującą się nadmierną proliferacją oraz zaburzeniem różnicowania keratynocytów. Keratynocyty łuszczycowe mają zmniejszoną zdolność do apoptozy, co może mieć duże znaczenie dla przerostu naskórka w łuszczycy. Zaburzenia apoptozy w łuszczycy dotyczą również komórek układu immunologicznego. W pracy omó-wiono podstawy procesu apoptozy, a także jej wybrane aspekty w patogenezie łuszczycy. ABStrActApoptosis is a physiological mechanism of programmed cell death, in contrast to necrosis, without eliciting an inflammatory response. It plays the key role in the functioning of different tissues and organs. The balance between proliferation and apoptosis of keratinocytes is important for epidermal maintenance of homeostasis. Dysfunctional apoptosis plays an important role in the development of several skin disorders. Diseases with an increase of apoptosis are usually acute, while those with inhibited apoptosis tend to be chronic. Psoriasis is an immune-mediated chronic inflammatory skin disease. It is characterized by keratinocyte hyperproliferation and abnormal differentiation. Psoriatic keratinocytes are resistant to apoptosis and this phenomenon can be the key event in psoriatic hyperplasia. Apoptosis disturbances can also affect immune cells involved in the pathogenesis of psoriasis. In this review, we describe the basic concept of apoptosis and its relevance in psoriatic pathogenesis.

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Section: Apoptoza W łUszczycyunclassified

Selected aspects of apoptosis in psoriasis

Myśliwiec¹,

Baran²,

Flisiak³

2017

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“…Uv exposure induces the local and systemic suppression of the inflammatory response. it induces t cells with suppressor activity, inhibits the function of antigen-presenting cells, and stimulates the release of immunosuppressive cytokines (4).…”

Section: Figmentioning

confidence: 99%

The Number of Immunoregulatory T Cells is Increased in Patients with Psoriasis after Goeckerman Therapy

Kondělková

Vokurková

Krejsek

et al. 2012

Acta Med. (Hradec Kralove, Czech Repub.)

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Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T-cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT, as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001).

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“…Using this technique we investigated a cohort of psoriatic patients treated with GT. In them, elevated level of BPDE-DNA adducts were previously found (20).…”

Section: Introductionmentioning

confidence: 97%

Droplet Digital PCR Analysis of GSTM1 Deletion Polymorphism in Psoriatic Subjects Treated with Goeckerman Therapy

Beránek

Fiala

Kremláček

et al. 2016

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary: Goeckerman therapy (GT) represents an effective treatment of psoriasis including a combination of pharmaceutical grade crude coal tar (CCT) and ultraviolet irradiation (UV-R). Coal tar contains a mixture of polycyclic aromatic hydrocarbons. The best known carcinogenic polyaromate -benzo [a]pyrene is metabolized into a highly reactive benzo [a] pyrene-7,8-diol-9,10-epoxide (BPDE). Glutathione S-transferase M1 (GSTM1) catalyses the conjugation of drugs, toxins and products of oxidative stress with glutathione. The aim of the study is to found possible associations between GSTM1 genotypes and the level of BPDE-DNA adducts in 46 psoriatic patients treated with GT. For genotyping, droplet digital PCR was applied. The GSTM1 copy number was normalized to β-globin reference gene. In five GSTM1*1/*1 subjects, the GSTM1 to β-globin ratio moved from 0.99 to 1.03 with a median of 1.01. GSTM1*0/*1 heterozygotes (n = 20) contained only one GSTM1 function allele which conditioned the ratio 0.47-0.53 (median 0.50). GSTM1*0/*0 individuals (n = 21) showed no amplification of the null variants because of the large deletion in GSTM1. BPDE-DNA concentrations ranged from 1.8 to 66.3 ng/µg with a median of 12.3 ng/µg. GSTM1*0/*0 and GSTM1*0/*1 genotypes showed non-significantly higher concentrations of BPDE-DNA adducts than the GSTM1*1/*1 one (12.3 and 12.4 vs 7.8 ng/µg). The non-significant relationship between BPDE-DNA adducts and GSTM1 genotypes in psoriatic patients could be associated with relatively low doses of CCT and short-term UV-R exposures used in GT.

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Genotoxic and apoptotic effects of Goeckerman therapy for psoriasis

Abstract: Our results demonstrate high dermal absorption of PAH during GT and provide evidence that GT promotes genotoxicity and apoptosis.

Cited by 18 publications

References 30 publications

Selected aspects of apoptosis in psoriasis

Selected aspects of apoptosis in psoriasis

The Number of Immunoregulatory T Cells is Increased in Patients with Psoriasis after Goeckerman Therapy

Droplet Digital PCR Analysis of GSTM1 Deletion Polymorphism in Psoriatic Subjects Treated with Goeckerman Therapy

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