metallothionein and Edema

Atopic dermatitis (AD), one of the most common chronic eczematous skin disorders, is associated with cutaneous hyperactivity as a response to environmental triggers. Metallothionein (MT) plays a constitutive defensive role in the response to noxious stimuli. However, the role of MT in AD development is unclear. Using an AD-like murine model created by the topical application of 2.4-dinitrofluorobenzene, we studied the dynamic pattern of MT expression on AD development. AD-like lesions were evaluated based on the development of erythema, edema, exfoliation, scaling, increased thickness, and increased weight of lesional skin. These characteristics of AD-like lesions and thymic stromal lymphopoietin (TSLP) expression peaked at Day 1 of the establishment of our model and gradually alleviated over time. The MT expression in lesional skin was increased and peaked at Day 3. By immunostaining, increased expression of MT was translocated from the cytoplasm to the nucleus. MT-1/2 knockout (MT-/-) mice and wild type (MT+/+) mice were also used to evaluate the role of MT on AD. MT-/- mice had greater edema scores, thickness, lesional skin weight, as well as more CD4+ T cells, TSLP, superoxide dismutase, and NDUFAF1. These results suggest that MT may play a protective role against AD development, and that antioxidant and nuclear protective mechanisms may be involved.

Topics: Animals; Antioxidants; CD4-Positive T-Lymphocytes; Dermatitis, Atopic; Dinitrofluorobenzene; Disease Models, Animal; Edema; Gene Expression Regulation; Humans; Metallothionein; Mice; Mice, Knockout; NADH Dehydrogenase; Superoxide Dismutase

The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune-modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV-induced immunosuppression, and against suppression induced by the mediator, cis-urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans.

Topics: Animals; Antioxidants; Beverages; Drinking; Edema; Female; Heme Oxygenase-1; Hypersensitivity; Immunosuppression Therapy; Inflammation; Lipid Peroxidation; Lycium; Metallothionein; Mice; Mice, Hairless; Oleic Acids; Oxidative Stress; Radiation Injuries, Experimental; Skin Diseases; Sunburn; Ultraviolet Rays

The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280-320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the post-irradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT-/-) observed after 3 x 3.4 kJ/m2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT+/+ mouse, the MT-/- mouse was significantly more immunosuppressed by moderate daily UVB doses (1. 75-5.9 kJ/m2). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT-/- mice was again markedly more suppressed than in MT+/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT+/+ mice, but to be absent in MT-/- epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.

Topics: Animals; Dermatitis, Contact; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Edema; Erythema; Immune Tolerance; Metallothionein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Skin; Ultraviolet Rays; Urocanic Acid