Successful treatment of lichen amyloidosis using a CO2 surgical laser.

Lichen amyloidosis (LA) is a type of primary localized cutaneous amyloidosis characterized by multiple pruritic discrete hyperkeratotic papules with amyloid deposition in the papillary dermis. Two patients with LA had been treated with topical corticosteroids, but with no effect on the eruptions. The present authors then started treating the affected area by superficial ablation using a CO2 surgical laser (LASER 30C, Lumenis Inc., Yokneum, Israel) at a setting of 10-15 watts with a 0.12-second pulse duration, 0.36-second rest duration, and 5-mm laser spot size. The present authors treated the patients twice a month with the CO2 laser. The papules on the legs had flattened in both patients, with a great improvement in the severe itching after 6 months in Case 1 and after 10 months in Case 2. These cases indicate that the CO2 laser led to a good response in terms of the clinical manifestations, and may be useful for the treatment of LA.

Involvement of MIF in basement membrane damage in chronically UVB-exposed skin in mice.

Solar ultraviolet (UV) B radiation is known to induce matrix metalloproteinases (MMPs) that degrade collagen in the basement membrane. Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that plays an essential role in the pathophysiology of skin inflammation induced by UV irradiation. This study examined the effects of MIF on basement membrane damage following chronic UVB irradiation in mice. The back skin of MIF transgenic (Tg) and wild-type (WT) mice was exposed to UVB three times a week for 10 weeks. There was a decrease in intact protein levels of type IV collagen and increased basement membrane damage in the exposed skin of the MIF Tg mice compared to that observed in the WT mice. Moreover, the skin of the MIF Tg mice exhibited higher MIF, MMP-2 and MMP-9 expression and protein levels than those observed in the WT mice. We also found that chronic UVB exposure in MIF Tg mice resulted in higher levels of neutrophil infiltration in the dermis compared with that observed in the WT mice. In vitro experiments revealed that MIF induced increases in the MMPs expression, including that of MMP-9 in keratinocytes and MMP-2 in fibroblasts. Cultured neutrophils also secreted MMP-9 stimulated by MIF. Therefore, MIF-mediated basement membrane damage occurs primarily through MMPs activation and neutrophil influx in murine skin following chronic UVB irradiation.

In vitro cytokine expression by peripheral mononuclear cells in herbal drug-induced skin eruption.

Herbal medicine is widely used worldwide and is associated with side-effects such as skin eruptions. Herbal drugs are often produced by combining multiple crude drugs, mostly of plant origin. Determining which medi-cinal plants are associated with the herbal drugs that induce skin eruptions can therefore be difficult. This study investigated mRNA expression of several cytokines in peripheral mononuclear cells (PBMCs) from two patients with herbal drug-induced skin eruptions; one reacted to keishi-bukuryo-gan (KBG), composed of 5 medicinal plants, and the other patient reacted to senna. PBMCs (1×106) from the 2 patients were cultured for 24 h with the supernatant from the medicinal plants from KBG or senna in various concentrations, and a reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. A high mRNA level of interleukin (IL)-4 and IL-5 was detected in PBMCs stimulated by KBG and two of its components. Senna stimulated a high level of IL-4 and IL-5 mRNA levels in PBMCs from patient with senna-induced drug reaction.

Synthesis and characterization of high-quality skin-cooling sheets containing thermosensitive poly(N-isopropylacrylamid).

Poly(N-isopropylacrylamide) (PNIPAAm) is the most popular thermosensitive polymer, and exhibits a low critical solution temperature of approximately 32°C. This study aimed to examine the usefulness of new cooling sheets, which are manufactured using a thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) material. We prepared cooling-hydrogel sheets containing PNIPAAm (PNIPAAm sheet). We measured the skin temperature on the arms of the subjects using a thermograph and compared the usefulness of the PNIPAAm sheet and a control cooling-hydrogel sheet that did not contain the PNIPAAm mixture. Thermographic measurements obtained 40 min after the treatment with the cooling sheets showed the skin temperature of the subjects treated with the 3.% (w/w) PNIPAAm sheets to be significantly lower than that of the subjects treated with the control cooling-hydrogel sheet (p < 0.005). Compared with the control sheet, the cooling effect of the new PNIPAAm sheet also persisted for a longer duration (up to 100 min). The PNIPAAm sheets exhibited excellent cooling effects. This sheet may therefore be useful for lowering the body temperature of patients with high-grade fever, such as fever due to influenza infection.

UV-B radiation induces macrophage migration inhibitory factor-mediated melanogenesis through activation of protease-activated receptor-2 and stem cell factor in keratinocytes.

UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF had no effect on the release of endothelin-1 or prostaglandin E2 in keratinocytes. In addition, MIF had no direct effect on melanin and tyrosinase synthesis in cultured human melanocytes. The effect of MIF on melanogenesis was also examined using a three-dimensional reconstituted human epidermal culture model, which is a novel, commercially available, cultured human epidermis containing functional melanocytes. Migration inhibitory factor induced an increase in melanin content in the epidermis after a 9-day culture period. Moreover, melanin synthesis induced by UV-B stimulation was significantly down-regulated by anti-MIF antibody treatment. An in vivo study showed that the back skin of MIF transgenic mice had a higher melanin content than that of wild-type mice after 12 weeks of UV-B exposure. Therefore, MIF-mediated melanogenesis occurs mainly through the activation of PAR-2 and SCF expression in keratinocytes after exposure to UV-B radiation.

Macrophage migration inhibitory factor is essential for eosinophil recruitment in allergen-induced skin inflammation.

Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine that has an essential role in the pathophysiology of experimental allergic inflammation. Recent findings suggest that MIF is involved in several allergic disorders, including atopic dermatitis (AD). In this study, the role of MIF in allergic skin inflammation was examined using a murine model of AD elicited by epicutaneous sensitization with ovalbumin (OVA). We observed the number of skin-infiltrating eosinophils to significantly increase in OVA-sensitized MIF transgenic (Tg) mice compared with their wild-type (WT) littermates. On the other hand, eosinophils were virtually absent from the skin of MIF knockout (KO) mice and failed to infiltrate their skin after repeated epicutaneous sensitization with OVA. The mRNA expression levels of eotaxin and IL-5 were significantly increased in OVA-sensitized skin sites of MIF Tg mice, but were significantly decreased in MIF KO mice in comparison with the levels in WT littermates. Eotaxin expression was induced by IL-4 stimulation in fibroblasts in MIF Tg mice, but not in MIF KO mice. These findings indicate that MIF can induce eosinophil accumulation in the skin. Therefore, the targeted inhibition of MIF might be a promising new therapeutic strategy for allergic skin diseases.

Macrophage migration inhibitory factor ameliorates UV-induced photokeratitis in mice.

Acute ultraviolet (UV) exposure causes photokeratitis, and induces apoptosis in corneal cells of the eye. Macrophage migration inhibitory factor (MIF) was originally identified as a lymphokine. Today, MIF is considered as an integral component of the host antimicrobial alarm system and stress response that promotes the proinflammatory functions of immune cells. Also, MIF is considered to contribute the wound healing process. The aim of the present study is to determine the effects of MIF expression on UV irradiated corneal damage. MIF transgenic (MIF-Tg), wild type (WT), and MIF deficient (MIF KO) mice were UVB-irradiated of 400mJ/cm2 to induce acute UV-photokeratitis. MIF Tg mice constitutively produce high levels of MIF. Morphological changes were most severe in MIF KO mice, and WT and MIF Tg mice were following. Corneal basement membrane of MIF-Tg was well preserved. Prominent higher level of MIF was observed in MIF-Tg than WT after UVB irradiation in cornea. TUNEL staining showed a significantly smaller number of TUNEL positive nuclei in MIF-Tgm (6.2+/-4.3 cells/section, p<0.01 compared with WT) than WT (30.7+/-9.1) and MIF KO mice (32.1+/-12.7) 24h after UV exposure. The number of c-Jun positive nuclei was significantly higher in MIF Tg (p<0.01) than in WT and MIF KO mice. Serial observation revealed that BrdU incorporation was significantly upregulated in MIF Tg (p<0.01), but downregulated in MIF KO (p<0.01) than WT mice. MIF expression may thus be related to the amelioration of UVB-caused corneal injury, and this association was attributable to the upregulation of cell proliferation after acute UV-induced corneal damage, which involves the c-Jun dependent pathway. In conclusion, UV-damaged cornea is recoverable without MIF, however it takes longer time than normal condition. Cornea is less damaged and can make a quick recovery when ocular tissue is enough supplied with MIF.

Desmoplastic fibroblastoma (collagenous fibroma).

Desmoplastic fibroblastoma (DF) is a rare fibrotic tumor that has a wide anatomic distribution and it can appear in deep sections of the subcutis, in fascia, in aponeurosis or in skeletal muscles. This report describes a case of DF that appeared on the left side of the neck of a 55-year-old male as a 3.5-cm solitary, firm nodule. Histologically, it was composed of stellate or bland spindle-shaped cells embedded in a loose collagenous stroma. The entrapment of fat and muscle tissues was focally identified at the edges of the tumor. The stellate and multinucleated cells in the lesion were strongly positive for vimentin but negative for cytokeratin, smooth muscle actin, desmin, S-100, CD34, factor XIIIa, and CD68. These findings suggest that the stellate and multinucleated cells in the lesion were of fibroblastic origin and this neoplasm was pathologically benign.

Interleukin-1beta and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression.

BACKGROUND: Exposure to solar UV radiation is the main environmental factor that causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member of the MMP family and degrades types I and III collagens, which are the major structural components of the dermis. OBJECTIVE: We evaluated the involvement IL-1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation. METHODS: IL-1beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs production. RESULTS: IL-1beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/beta-deficient mice produced significantly decreased levels of MMPs compared to wild-type mice after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much less sensitive to IL-1beta-induced MMPs production. On the contrary, IL-1beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta stimulation was found to be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK inhibitor and inhibitor were found to have little effect on expression of MMP-1 mRNA. CONCLUSIONS: IL-1beta is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and contribute to the loss of interstitial collagen in skin photoaging.

Presence of circulating CCR10+ T cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides.

PURPOSE: Mycosis fungoides (MF), a common type of cutaneous T cell lymphoma with an indolent clinical course, has the characteristic that malignant T cell clones are recruited into the skin from the early disease stages. The mechanisms of recruitment have been suggested from our knowledge of various chemokine-chemokine receptor interactions. Recently, CCR10 and CTACK/CCL27 were proposed to play a role in the recruitment of other types of cutaneous T cell lymphoma. We examined the expression of CCR10 in peripheral blood and serum CTACK/CCL27 levels in patients with MF. EXPERIMENTAL DESIGN: Eighteen patients with MF, six patients with atopic dermatitis, and nine healthy volunteers were enrolled in our investigation. We investigated the differences in CCR10+ CD4+ expression in peripheral blood mononuclear cells by flow cytometry. Serum CTACK/CCL27 levels were determined using a CTACK/CCL27 ELISA assay kit. RESULTS: The number of circulating CCR10+ CD4+ cells was significantly higher in MF peripheral blood than in controls, even during the early stages. In lesional MF skin, infiltrating tumor cells also showed extensive expression of CCR10. The serum level of CTACK/CCL27 was higher in patients with MF than normal controls, but no statistical difference was found compared with atopic dermatitis patients. CONCLUSIONS: CCR10-CTACK/CCL27 interactions between circulating T cells and keratinocytes would seem to play an important role in the pathophysiology of MF from the early disease stages.