Expression of metallothioneins‐I and ‐II isoforms at positive patch‐test sites

Abstract

The expression and the distribution of metallothioneins (MT)-I and II isoforms were evaluated in 5 healthy volunteers and in 16 subjects with positive patch test reactions to various compounds. Skin specimens taken both from the healthy skin of the back and at positive patch test sites (at 48 h), were treated using a 3-step indirect immunoperoxidase procedure with a mouse monoclonal IgG1 antibody reactive against I and II isoforms of human, rat and horse MT. MT were expressed in the basal layer of the healthy skin of both controls and sensitive subjects, without any significant difference. At positive patch test sites, there was an overexpression of MT in basal and suprabasal layers of the epidermis. Overexpression of MT, related to the degree of the inflammatory reactions elicited by the penetrating compounds was observed in the dermis. The cells expressing MT in the dermis were mostly T lymphocytes and cells with dendritic morphology which positively stained in part for CD34 and in part for XIIIa markers and negatively for KP1, S100 and HLA-DR. Taken together, these results seem to indicate that MT represent a constitutive mechanism of defence expressed by different types of cells in the skin, which is triggered by contact with both metallic and non-metallic compounds. The biological significance of MT in the skin remains to be elucidated. Our preliminary findings do not permit evaluation of whether these nearly ubiquitous proteins exert their cytoprotective effects in the skin acting simultaneously as antioxidant, metal binding or zinc suppliers, or if they display these activities mainly depending on the nature of the penetrating substances.

Metallothionein I and II gene knock-out mice exhibit reduced tolerance to 24-h sodium lauryl sulphate patch testing

“…The role of MTs in skin inflammation has also been studied. Upregulation of MT proteins can be found at positive allergy patch‐test sites 5 . Knockout mice for MT genes I and II (MT –/– ) exhibit reduced tolerance to ultraviolet B injury in vivo , 6 suggesting that the MT genes have a photoprotective role in mice.…”

“…Upregulation of MT proteins can be found at positive allergy patch-test sites. 5 Knockout mice for MT genes I and II (MT -⁄ -) exhibit reduced tolerance to ultraviolet B injury in vivo, 6 suggesting that the MT genes have a photoprotective role in mice. MTs may also have a protective role in skin irritation, as topical MT solutions can shorten the healing time of partial-thickness burn injuries.…”

Metallothioneins: potential therapeutic aids for wound healing in the skin

“…Transforming growth factor‐beta, which is known to antagonize epidermal growth factor, blocked both the MT‐gene expression and the stimulation of DNA‐synthesis. Other indirect experimental evidence suggests that MT is involved in the regulation of the inflammatory response in wound repair, possibly through its cytokine action, interaction with nitric oxide, 28 or through immunological changes 7,8 . Interleukin‐1 (IL‐1) production is triggered by cellular damage, infection, or toxic change leading to a wide spectrum of host responses 20 .…”

“…Additionally, MTs are known to modulate the release of gaseous mediators including nitric oxide in damaged tissue and to influence inflammation and apoptosis 6 . Evidence also shows that MT may be involved in the immune response, influencing the release and cellular modulation of the pro‐inflammatory cytokines interleukin‐6 and tumor necrosis factor‐alpha, in the pathogenesis of experimental auto‐immune diseases like encephalomyelitis 7,8 …”

“…6 Evidence also shows that MT may be involved in the immune response, influencing the release and cellular modulation of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, in the pathogenesis of experimental autoimmune diseases like encephalomyelitis. 7,8 Available research shows that mammalian MTs are composed of 61-62 amino acids with cysteine residues underpinning the metal binding properties ascribed to MT-1 and MT-2. A total of four MT-isoforms have been characterized so far, with MT-1 and MT-2 prevalent in epithelial tissues such as skin, intestinal mucosa, and liver, MT-3 in the brain, and MT-4 isolated from squamous epithelia (tongue).…”