title: IKKbeta leads to an inflammatory skin disease resembling interface dermatitis.
abstract: IKKbeta is a subunit of the IkappaB kinase (IKK) complex required for NF-kappaB activation in response to pro-inflammatory signals. NF-kappaB regulates the expression of many genes involved in inflammation, immunity, and apoptosis, and also controls cell proliferation and differentiation in different tissues; however, its function in skin physiopathology remains controversial. In this study we report the alterations caused by increased IKKbeta activity in skin basal cells of transgenic mice. These animals suffered chronic inflammation with abundant macrophages and other CD45(+) infiltrating cells in the skin, which resulted in epidermal basal cell injury and degeneration of hair follicles. They showed histological features characteristic of interface dermatitis (ID). This phenotype is accompanied by an increased production of inflammatory cytokines by transgenic keratinocytes. Accordingly, transcriptome studies show upregulation of genes associated with inflammatory responses. The inflammatory phenotype observed as a consequence of IKKbeta overexpression is independent of T and B lymphocytes, as it also arises in mice lacking these cell types. In summary, our data indicate the importance of IKKbeta in the development of ID and in the homeostasis of stratified epithelia. Our results also support the idea that IKKbeta might be a valid therapeutic target for the treatment of skin inflammatory diseases.
authors.affiliation: Department of Epithelial Biomedicine, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Avda. Complutense 22, Madrid, Spain.
authors.forename: Angustias
authors.initials: A
authors.lastname: Page
authors.forename: Manuel
authors.initials: M
authors.lastname: Navarro
authors.forename: Marina
authors.initials: M
authors.lastname: Garín
authors.forename: Paloma
authors.initials: P
authors.lastname: Pérez
authors.forename: M Llanos
authors.initials: ML
authors.lastname: Casanova
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Moreno
authors.forename: José L
authors.initials: JL
authors.lastname: Jorcano
authors.forename: José L
authors.initials: JL
authors.lastname: Cascallana
authors.forename: Ana
authors.initials: A
authors.lastname: Bravo
authors.forename: Angel
authors.initials: A
authors.lastname: Ramírez
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003872:Dermatitis / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000378:metabolism*; D007107:Immune System / Q000276:immunology* / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D016328:NF-kappa B; D051550:I-kappa B Kinase; C496560:IKBKB protein, human