ABSTRACT
Atopic dermatitis (AD) is a chronic inflammatory skin disease. A hallmark of AD is dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds. However, effects of A vera on AD were not fully elucidated. In this study, we investigated the oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)-induced AD in mice. Oral administration of PAG suppressed total and OVA-specific IgE production in sera and decreased the epidermal thickness of skin. Numbers of Ki-67-positive cells were reduced by PAG treatment. Expression levels of tight junction genes, including those that encode ZO-1, Claudin-1 and Claudin-8, were decreased in AD skin lesions, whereas oral administration of PAG partially restored the expression levels of tight junction genes. In addition, IL-4 and IL-17A mRNA transcript levels were reduced in skin lesions after PAG treatment. Taken together, our findings suggest that oral administration of PAG ameliorated AD, normalized tight junction gene expression and suppressed inflammatory cytokines in AD skin.
Subject(s)
Aloe/chemistry , Anti-Allergic Agents/pharmacology , Dermatitis, Atopic/etiology , Plant Exudates/pharmacology , Polysaccharides/pharmacology , Tight Junctions/drug effects , Tight Junctions/immunology , Animals , Anti-Allergic Agents/chemistry , Biomarkers , Cytokines/metabolism , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/pathology , Disease Models, Animal , Disease Progression , Female , Inflammation Mediators/metabolism , Keratinocytes/drug effects , Keratinocytes/immunology , Keratinocytes/metabolism , Mice , Ovalbumin/adverse effects , Plant Exudates/chemistry , Polysaccharides/chemistry , Skin/drug effects , Skin/immunology , Skin/metabolism , Skin/pathologyABSTRACT
Adult stem cells are multipotent and self-renewing cells that contain several functions; i) migration and homing potential: stem cells can migrate to injured and inflamed tissues. ii) differentiation potential: stem cells which migrated to injured tissues can be differentiated into multiple cell types for repairing and regenerating the tissues. iii) immunomodulatory properties: stem cells, especially mesenchymal stem cells can suppress immune system such as inflammation. All those characteristics might be useful for the treatment of the digestive tract diseases which are complex and encompass a broad spectrum of different pathogenesis. Preclinical stem cell therapy showed some promising results, especially in liver failure, pancreatitis, sepsis, and inflammatory bowel disease. If we can understand more about the mechanism of stem cell action, stem cell therapy can become a promising alternative treatment for refractory digestive disease in the near future. In this review, we summarized current preclinical experiences in diseases of the digestive tract using stem cells. (Korean J Gastroenterol 2011;58:133-138).
Subject(s)
Adult Stem Cells/transplantation , Digestive System Diseases/therapy , Adult Stem Cells/cytology , Drug Evaluation, Preclinical , HumansABSTRACT
Tagging the cell surface receptor with ubiquitin is believed to provide a signal for the endocytic pathway. E3 ubiquitin ligases such as Cbl-b and Itch have been implicated in T cell activation and tolerance induction. However, the underlying mechanisms remain unclear. We describe that in mice deficient in the E3 ubiquitin ligases Cbl-b and Itch, T cell activation was augmented, accompanied by spontaneous autoimmunity. The double-mutant T cells exhibited increased phosphorylation of the T cell receptor-zeta (TCR-zeta) chain, whereas the endocytosis and stability of the TCR complex were not affected. TCR-zeta was polyubiquitinated via a K33-linkage, which affected its phosphorylation and association with the zeta chain-associated protein kinase Zap-70. The juxtamembrane K54 residue in TCR-zeta was identified to be a primary ubiquitin conjugation site, whose mutation increased its phosphorylation and association of TCR-zeta and Zap-70. Thus, the present study reveals unconventional K33-linked polyubiquitination in nonproteolytic regulation of cell-surface-receptor-mediated signal transduction.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Proto-Oncogene Proteins c-cbl/genetics , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/metabolism , Ubiquitin-Protein Ligases/genetics , Animals , Autoimmunity/genetics , Endocytosis/immunology , Humans , Jurkat Cells , Lymphocyte Activation/genetics , Lysine/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Mutagenesis, Site-Directed , Mutation/genetics , Protein Binding , Receptors, Antigen, T-Cell/genetics , Signal Transduction/immunology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Ubiquitination/genetics , ZAP-70 Protein-Tyrosine Kinase/metabolismABSTRACT
The 12/15-lipoxygenase (12/15-LOX) pathways of arachidonate metabolism have been implicated in the pathogenesis of psoriasis. Since UV photo-therapy is a commonly used technique for inhibiting cell proliferation and inflammation in skin diseases, we hypothesized that UV-irradiation may affect 12/15-LOX expression which might regulate cell proliferation. In this study, we showed that UV-irradiation suppressed 12-LOX expression, whereas up-regulated 15-LOX expression. Treatment with the 15-LOX metabolites sufficiently suppressed insulin-like growth factor II-induced 12-LOX expression and blocked cell cycle progression. On the basis of our findings, we think that the 15-LOX metabolites may inhibit epidermal hyperplasia in psoriasis by regulating 12-LOX expression.