Transcriptional responses of human epidermal keratinocytes to cytokine interleukin-1.
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-1alpha. 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 TNFalpha and IFNgamma regulated ones showed more similarities between IL-1 and TNFalpha than IL-1 and IFNgamma, 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.
Yano
Shoichiro
S
Department of Dermatology, NYU School of Medicine, New York 10016, USA.
Banno
Tomohiro
T
Walsh
Rebecca
R
Blumenberg
Miroslav
M
D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D016650:Fluorescein-5-isothiocyanate; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018075:RNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D023083:beta-Defensins / Q000378:metabolism
D015415:Biomarkers; C106641:DEFB4A protein, human; D005456:Fluorescent Dyes; D007375:Interleukin-1; D016328:NF-kappa B; D018075:RNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins; D023083:beta-Defensins; D016650:Fluorescein-5-isothiocyanate