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Establishing an effective epidermal barrier requires a series of coordinated molecular events involving keratinocytes (KCs) within a stratified epithelium. Epidermal maturation depends on convergence of pathways involving components of. NF-κB and peroxisome proliferator activated receptor (PPAR) signaling systems that promote terminal differentiation and production of a stratum corneum. The Notch-1 receptor and its ligand Delta-1 have been proposed by others to participate in early events in KC differentiation. Here, we establish differential expression patterns for several Notch receptors and ligands in normal human skin. These immunolocalization findings, together with functional studies demonstrating increased levels of Notch ligand/receptors occurring during the onset of differentiation, prompted use of a soluble Notch ligand, a peptide derived from the most conspicuously expressed ligand in skin, Jagged-l. Exposing submerged KC monolayers to this peptide (JAG-l) in co-presence of elevated calcium ion concentration, produced stratification with Ioricrin expression. Using a living human epidermal equivalent (EE) model system, when submerged cultures were raised to an air/liquid interface to generate a fully mature epidermis, activation of Notch signaling was detected. Addition of JAG-1 peptide to submerged EEs was sufficient to induce epidermal maturation. Moreover, a soluble decoy Notch inhibitor prevented such differentiation and corneogenesis in human EEs exposed to either an air/liquid interface or to the JAG-1 peptide, in KC monolayers, addition of JAG-1 peptide induced IKKα mediated NF-κB activation, as well as increased PPARγ expression. Immunoprecipitation/Western blot analysis revealed a physical association between the p65 subunit of NFκB and PPARγ. These results indicate that activation of Notch signaling is necessary for maturation of human epidermis, and activation by a soluble Notch ligand is sufficient to... [ABSTRACT FROM AUTHOR]

Focuses on several viewpoints on the function of skin. Integral component of the immune, nervous and endocrine systems; Maintenance of temperature, electrolyte and fluid balance; Reflection on the full range of skin functions.

Examines the role of protein kinase C activation in caspase activation and disruption of mitochondria function by ultraviolet radiation. Expression of active catalytic domain; Catalysis-induced apoptosis.

With indirect immunofluorescence techniques we demonstrated that recombinant gamma-interferon induced the expression of the class II antigens HLA-DR and HLA-DQ as well as intercellular adhesion molecule-1 (ICAM-1) on normal, cultured human keratinocytes grown in low-calcium, serum-free medium. Each antigen displayed a distinctive cellular staining pattern. HLA-DR was strongly localized to perinuclear zones with intense cell surface expression; HLA-DQ displayed a perinuclear accentuation, but with minimal cell surface staining, and ICAM-1 was strongly expressed in a diffuse cytoplasmic pattern with intense cell surface expression. Keratinocytes grown in medium supplemented with 10% fetal calf serum underwent differentiation, with a diminished expression of all three antigens as compared to those grown in low-calcium, serum-free medium. These results confirm that gamma interferon can differentially regulate HLA-DR and HLADQ expression; that there are probably different biochemical metabolic pathways by which these three molecules are expressed on keratinocytes, and that the expression is also a function of the degree of keratinocyte differentiation. The strong cell surface expression of ICAM-1 is suggested to be of major importance as the recognition molecule, by which T cells bind to gamma interferon exposed keratinocytes, and suggests an integral role for this molecule in epidermal lymphocyte trafficking. [ABSTRACT FROM AUTHOR]

We investigated the in vivo effect of recombinant interferon-γ (IFN-γ) and tumour necrosis factor α (TNF-α) treatment of mice on the development of the delayed-type hypersensitivity (DTH) reaction and lichenoid tissue reaction (LTR) following the local injection of cloned autoreactive T cells. Both the DTH reaction and the LTR were significantly enhanced by pre- treatment with IFN-γ, but not with TNF-α. Induction of class II MHC antigens on keratinocytes was not essential for the enhancement by IFN-γ. Administration of anti-IFN-γ antibody reduced the DTH reaction and LTR, although complete inhibition was not observed with our treatment regimen. The ability of I FN-γ to increase the number of the cloned T cells invading the epidermis in vivo, is in keeping with our previous observation that IFN-γ treatment of cultured keratinocytes markedly increased the adherence reaction between T cells and keratinocytes in vitro. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about expression of the myelomonocytic antigens in human epidermis.