Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases

Gillian Smith, C. Roland Wolf, Yusuf Y. Deeni, Robert S. Dawe, Alan T. Evans, Muriel M. Comrie, James Ferguson, Sally H. Ibbotson

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Abstract

Background

Treatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemo-therapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies.

Methods

We used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis.

Findings

We found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3·38 [95% CI 2·64–4·34] times higher; p<0·0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme.

Interpretation

These findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

Original languageEnglish
Pages (from-to)1336-1343
Number of pages8
JournalThe Lancet
Volume361
Issue number9366
DOIs
StatePublished - 19 Apr 2003

Fingerprint

Psoriasis
Skin Diseases
Individuality
Cytochrome P-450 Enzyme System
Skin
Tretinoin
Ficusin
Radiation
Enzymes
Coal Tar
Enzyme Induction
Photochemotherapy
Real-Time Polymerase Chain Reaction
Healthy Volunteers
Gene Expression
Liver
Handling (Psychology)

Cite this

Smith, Gillian; Wolf, C. Roland; Deeni, Yusuf Y.; Dawe, Robert S.; Evans, Alan T.; Comrie, Muriel M.; Ferguson, James; Ibbotson, Sally H. / Cutaneous expression of cytochrome P450 CYP2S1 : individuality in regulation by therapeutic agents for psoriasis and other skin diseases.

In: The Lancet, Vol. 361, No. 9366, 19.04.2003, p. 1336-1343.

Research output: Contribution to journalArticle

@article{afbdd2e28cc34d079a8f6ca014857aec,
title = "Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases",
abstract = "BackgroundTreatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemo-therapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies.MethodsWe used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis.FindingsWe found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3·38 [95% CI 2·64–4·34] times higher; p<0·0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme.InterpretationThese findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.",
author = "Gillian Smith and Wolf, {C. Roland} and Deeni, {Yusuf Y.} and Dawe, {Robert S.} and Evans, {Alan T.} and Comrie, {Muriel M.} and James Ferguson and Ibbotson, {Sally H.}",
year = "2003",
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doi = "10.1016/S0140-6736(03)13081-4",
volume = "361",
pages = "1336--1343",
journal = "The Lancet",
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Smith, G, Wolf, CR, Deeni, YY, Dawe, RS, Evans, AT, Comrie, MM, Ferguson, J & Ibbotson, SH 2003, 'Cutaneous expression of cytochrome P450 CYP2S1: individuality in regulation by therapeutic agents for psoriasis and other skin diseases' The Lancet, vol 361, no. 9366, pp. 1336-1343. DOI: 10.1016/S0140-6736(03)13081-4

Cutaneous expression of cytochrome P450 CYP2S1 : individuality in regulation by therapeutic agents for psoriasis and other skin diseases. / Smith, Gillian; Wolf, C. Roland; Deeni, Yusuf Y.; Dawe, Robert S.; Evans, Alan T.; Comrie, Muriel M.; Ferguson, James; Ibbotson, Sally H.

In: The Lancet, Vol. 361, No. 9366, 19.04.2003, p. 1336-1343.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cutaneous expression of cytochrome P450 CYP2S1

T2 - The Lancet

AU - Smith,Gillian

AU - Wolf,C. Roland

AU - Deeni,Yusuf Y.

AU - Dawe,Robert S.

AU - Evans,Alan T.

AU - Comrie,Muriel M.

AU - Ferguson,James

AU - Ibbotson,Sally H.

PY - 2003/4/19

Y1 - 2003/4/19

N2 - BackgroundTreatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemo-therapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies.MethodsWe used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis.FindingsWe found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3·38 [95% CI 2·64–4·34] times higher; p<0·0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme.InterpretationThese findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

AB - BackgroundTreatment of common skin diseases such as psoriasis is complicated by differences between individuals in response to topical drug treatment and photochemo-therapy. Individuality in hepatic expression of drug-metabolising enzymes is an important determinant of systemic drug handling; we investigated whether similar variation in cutaneous gene expression contributes to individuality in response to topical therapies.MethodsWe used quantitative real-time RT-PCR to demonstrate the expression in skin of a recently identified cytochrome P450, CYP2S1, in healthy volunteers (n=27) and patients with psoriasis (n=29). We also investigated regulation of CYP2S1 by ultraviolet radiation, psoralen-ultraviolet A (PUVA), and topical drugs used to treat psoriasis.FindingsWe found that CYP2S1 is expressed in skin and showed pronounced individuality in constitutive expression of the enzyme and its induction after ultraviolet irradiation or topical drug treatment. Cutaneous expression of CYP2S1 was induced by ultraviolet radiation, PUVA, coal tar, and all-trans retinoic acid; expression was significantly higher in lesional psoriatic skin than in adjacent non-lesional skin (geometric mean 3·38 [95% CI 2·64–4·34] times higher; p<0·0001), which implies that topical drugs are differentially metabolised in psoriatic plaque and non-lesional skin. We showed that all-trans retinoic acid is metabolised by CYP2S1, which has higher cutaneous expression than CYP26, previously described as the specific cutaneous P450 retinoic-acid-metabolising enzyme.InterpretationThese findings increase our understanding of the interaction between therapeutic agents and the skin and suggest a functional role for CYP2S1 in the metabolism of topical drugs and in mediating the response to photochemotherapy in psoriasis.

U2 - 10.1016/S0140-6736(03)13081-4

DO - 10.1016/S0140-6736(03)13081-4

M3 - Article

VL - 361

SP - 1336

EP - 1343

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9366

ER -