Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris
- 6 April 2004
- journal article
- Published by Oxford University Press (OUP) in British Journal of Dermatology
- Vol. 150 (4) , 668-676
- https://doi.org/10.1111/j.0007-0963.2004.05891.x
Abstract
Background Type 1 T cells are hypothesized to be central in the immunopathogenesis of psoriasis. Through elaboration of interferon (IFN)-γ, type 1 T cells regulate the expression of many ‘downstream’ inflammatory genes, including an array of chemokines that regulate leucocyte trafficking and activation in skin lesions. Accordingly, disease progression and/or severity might be controlled by the degree to which differing cytokines and chemokines are overexpressed in focal skin regions. To examine this possibility, we studied two forms of chronic psoriasis vulgaris that differ significantly in overall severity and progression: small plaque (SP) psoriasis occurring in Korean patients, and large plaque (LP) psoriasis occurring in North American patients. Objectives To characterize LP and SP psoriasis vulgaris with respect to expression of proinflammatory genes that define the type 1 T-cell axis in skin lesions [genes encoding interleukin (IL)-12, IFN-γ, and IFN-γ-regulated chemokines or inflammatory mediators]. Methods Total cellular RNA of skin samples from groups of patients with LP or SP psoriasis was analysed by quantitative reverse transcription-polymerase chain reaction (TaqMan analysis) to compare the differences in mRNA expression of genes related to the IFN-γ pathway. Results The mRNA expression of keratin 16, CD25, IFN-γ, IL-12 p40, signal transducer and activator of transcription-1, inducible nitric oxide synthase, IL-8, macrophage inflammatory protein-3α, monocyte chemoattractant protein-1, S100A12, IFN-γ-inducible protein of 10 kDa, IFN-inducible T-cell α-chemoattractant and monokine induced by IFN-γ was increased in the lesions of both LP psoriasis and SP psoriasis. However, IL-18 mRNA expression was significantly different in the lesions of LP psoriasis in comparison with those of SP psoriasis. Conclusions The results indicate that proinflammatory type 1 genes regulated by IFN-γ are similarly increased in both SP and LP psoriasis, but a potential difference in IL-18 exists between these disease forms. The consistent activation of this set of genes argues for a central role of IFN-γ as a molecular regulator of inflammation in these distinct subtypes of psoriasis vulgaris. In contrast, disease extent/severity must be controlled by yet other factors.Keywords
This publication has 34 references indexed in Scilit:
- The A5.1 allele of the major histocompatibility complex class I chain-related gene A is associated with psoriasis vulgaris in ChineseBritish Journal of Dermatology, 2000
- Calgranulin C is Overexpressed in Lesional PsoriasisJournal of Investigative Dermatology, 2000
- Role of neutrophils in induction of acute inflammation in T‐cell‐mediated immune dermatosis, psoriasis: A neutrophil‐associated inflammation‐boosting loopExperimental Dermatology, 2000
- The Association of Psoriasis with Human Leukocyte Antigens in Korean Population and the Influence of Age of Onset and SexJournal of Investigative Dermatology, 2000
- Counterregulation of Interleukin-18 mRNA and Protein Expression During Cutaneous Wound Repair in MiceJournal of Investigative Dermatology, 1999
- CELLULAR RESPONSES TO INTERFERON-γAnnual Review of Immunology, 1997
- Both psoriasis and benign migratory glossitis are associated with HLA-Cw6British Journal of Dermatology, 1996
- Intralesional T-Lymphocyte Activation as a Mediator of Psoriatic Epidermal Hyperplasia.Journal of Investigative Dermatology, 1995
- Cytokine‐induced expression of an inducible type of nitric oxide synthase gene in cultured vascular smooth muscle cellsFEBS Letters, 1993
- Lymphocyte Trafficking in Psoriasis: A New Perspective Emphasizing the Dermal Dendrocyte with Active Dermal Recruitment Mediated Via Endothelial Cells Followed by Intra-Epidermal T-Cell ActivationJournal of Investigative Dermatology, 1990