Cytokine Milieu of Atopic Dermatitis, as Compared to Psoriasis, Skin Prevents Induction of Innate Immune Response Genes

Journal of Immunology - Tập 171 Số 6 - Trang 3262-3269 - 2003
Ichiro Nomura1, Elena Goleva1, Michael Howell1, Q Hamid2, Peck Y. Ong1, Clifton F. Hall1, Marc A. Darst3, Bifeng Gao4, Mark Boguniewicz1, Jeffrey B. Travers3, Donald Y.M. Leung1
1*Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, and Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO 80262;
2Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada
3‡Departments of Dermatology and Pediatrics and the H. B. Wells Center for Pediatric Research, Pharmacology, and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202; and
4§Microarray Core Laboratory, University of Colorado Health Sciences Center, Denver, CO 80262

Tóm tắt

AbstractAtopic 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.

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Journal of Immunology

Tập 171 Số 6

3262-3269

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