Transcriptional responses of human epidermal keratinocytes to cytokine interleukin‐1

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Abstract
Interleukin‐1 is a proinflammatory and immunomodulatory cytokine that plays a crucial role in inflammatory diseases of the skin, including bacterial infections, bullous diseases, UV damage, and especially psoriasis. To characterize the molecular effects of IL‐1 in epidermis, we defined the transcriptional changes in human epidermal keratinocytes 1, 4, 24, and 48 h after treatment with IL‐1α. IL‐1 significantly regulated 388 genes, including genes associated with proteolysis, adhesion, signal transduction, proliferation, and epidermal differentiation. IL‐1 induces many genes that have antimicrobial function. Secreted cytokines, chemokines, growth factors, and their receptors are the prominent targets of IL‐1 regulation, including IL‐8, IL‐19, elafin, C3, and S100A proteins, which implicate IL‐1 in the pathogenesis of inflammatory diseases. IL‐1 induced not only proliferation‐associated genes but also differentiation marker genes such as transglutaminase‐1 and involucrin, which suggests that IL‐1 plays an important role in the aberrant proliferation and differentiation seen in psoriasis. Correlation of IL‐1 regulated genes with the TNFα and IFNγ regulated ones showed more similarities between IL‐1 and TNFα than IL‐1 and IFNγ, whereas Oncostatin‐M (OsM) affected a largely unrelated set of genes. IL‐1 regulates many genes previously shown to be specifically over‐expressed in psoriasis. In summary, IL‐1 regulates a characteristic set of genes that define its specific contribution to inflammation and aberrant differentiation in skin diseases. J. Cell. Physiol. 214:1–13, 2008.