Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes

Ichiro Nomura, Elena Goleva, Michael D. Howell, Quatyba A. Hamid, Peck Y. Ong, Clifton F. Hall, Marc A. Darst, Bifeng Gao, Mark Boguniewicz, Jeffrey Travers, Donald Y M Leung

Research output: Contribution to journalArticle

568 Citations (Scopus)

Abstract

Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human β defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-α IFN-γ, and IL-1β. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-α- and IFN-γ-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-α and IFN-γ under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.

Original languageEnglish
Pages (from-to)3262-3269
Number of pages8
JournalJournal of Immunology
Volume171
Issue number6
StatePublished - Sep 15 2003

Fingerprint

Atopic Dermatitis
Psoriasis
Innate Immunity
Cytokines
Skin
Genes
Ligases
Interleukin-8
Interleukin-13
Interleukin-4
Real-Time Polymerase Chain Reaction
Defensins
Infection
Interleukin-1
Keratinocytes
Skin Diseases
Chronic Disease
Up-Regulation
Immunohistochemistry
Biopsy

ASJC Scopus subject areas

  • Immunology

Cite this

Nomura, I., Goleva, E., Howell, M. D., Hamid, Q. A., Ong, P. Y., Hall, C. F., ... Leung, D. Y. M. (2003). Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. Journal of Immunology, 171(6), 3262-3269.

Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. / Nomura, Ichiro; Goleva, Elena; Howell, Michael D.; Hamid, Quatyba A.; Ong, Peck Y.; Hall, Clifton F.; Darst, Marc A.; Gao, Bifeng; Boguniewicz, Mark; Travers, Jeffrey; Leung, Donald Y M.

In: Journal of Immunology, Vol. 171, No. 6, 15.09.2003, p. 3262-3269.

Research output: Contribution to journalArticle

Nomura, I, Goleva, E, Howell, MD, Hamid, QA, Ong, PY, Hall, CF, Darst, MA, Gao, B, Boguniewicz, M, Travers, J & Leung, DYM 2003, 'Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes', Journal of Immunology, vol. 171, no. 6, pp. 3262-3269.
Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. Journal of Immunology. 2003 Sep 15;171(6):3262-3269.
Nomura, Ichiro ; Goleva, Elena ; Howell, Michael D. ; Hamid, Quatyba A. ; Ong, Peck Y. ; Hall, Clifton F. ; Darst, Marc A. ; Gao, Bifeng ; Boguniewicz, Mark ; Travers, Jeffrey ; Leung, Donald Y M. / Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. In: Journal of Immunology. 2003 ; Vol. 171, No. 6. pp. 3262-3269.
@article{1e35725145c44cb083954a36f3a414f6,
title = "Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes",
abstract = "Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human β defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-α IFN-γ, and IL-1β. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-α- and IFN-γ-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-α and IFN-γ under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.",
author = "Ichiro Nomura and Elena Goleva and Howell, {Michael D.} and Hamid, {Quatyba A.} and Ong, {Peck Y.} and Hall, {Clifton F.} and Darst, {Marc A.} and Bifeng Gao and Mark Boguniewicz and Jeffrey Travers and Leung, {Donald Y M}",
year = "2003",
month = "9",
day = "15",
language = "English",
volume = "171",
pages = "3262--3269",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

TY - JOUR

T1 - Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes

AU - Nomura, Ichiro

AU - Goleva, Elena

AU - Howell, Michael D.

AU - Hamid, Quatyba A.

AU - Ong, Peck Y.

AU - Hall, Clifton F.

AU - Darst, Marc A.

AU - Gao, Bifeng

AU - Boguniewicz, Mark

AU - Travers, Jeffrey

AU - Leung, Donald Y M

PY - 2003/9/15

Y1 - 2003/9/15

N2 - Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human β defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-α IFN-γ, and IL-1β. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-α- and IFN-γ-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-α and IFN-γ under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.

AB - Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human β defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-α IFN-γ, and IL-1β. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-α- and IFN-γ-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-α and IFN-γ under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.

UR - http://www.scopus.com/inward/record.url?scp=0041331649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0041331649&partnerID=8YFLogxK

M3 - Article

C2 - 12960356

AN - SCOPUS:0041331649

VL - 171

SP - 3262

EP - 3269

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 6

ER -