Monocytes play a critical role in chronic atopic dermatitis (AD) and are the primary leukocytes that interact with activated platelets. Although activated platelets release a variety of mediators, the role of platelets in cutaneous allergic inflammation remains unclear. Serotonin (5-hydroxytryptamine, 5-HT) is one of the prototypic mediators produced by activated platelets. We examined the effect of 5-HT on the function and lifespan of human monocytes. Normal human monocytes treated with 5-HT exhibited upregulated expression of costimulatory molecules, enhanced capacity to produce cytokines following lipopolysaccharide treatment, and to stimulate allogeneic CD4+ T cells. 5-HT also attenuated the apoptosis in normal human monocytes in a dose-dependent manner. The plasma levels of 5-HT were increased in patients with AD compared with controls and correlated with the SCORAD index. 5-HT also inhibited monocyte apoptosis in these patients. 5-HT upregulated Bcl-2 and Mcl-1, and inhibited the activation of caspase-3. The effects of 5-HT on monocyte apoptosis were mediated by the 5-HT1 and/or 5-HT7 receptors. 5-HT and a 5-HT(1/6/7)-receptor agonist induced phosphorylation of extracellular signal-regulated kinase1/2 and activation of nuclear transcription factor-kappaB. These findings support that 5-HT activates monocytes and inhibits apoptosis, allowing them to remain in the tissue and contribute to chronic inflammation.

SummaryThe local cytokine environment and presence of stimulatory signals determine whether monocytes acquire dendritic cell (DC) or macrophage characteristics and functions. Because enhanced platelet activation is reported in patients with many allergic disorders, such as atopic dermatitis, plateletderived factors may influence monocytic differentiation into DC. In this study we examined the effect of serotonin, a prototypic mediator of allergic inflammation released mainly by activated platelets at the inflammatory site, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived DC. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of serotonin, and the phenotypes and function of these cells were analysed. In the presence of serotonin, monocytes differentiated into DC with reduced expression of co-stimulatory molecules and CD1a, whereas expression of CD14 was increased. These serotonin-treated DC exhibited significantly reduced stimulatory activity toward allogeneic T cells. However, these cells showed enhanced cytokine-producing capacity, including IL-10 but not IL-12. There was no significant difference between both types of DC in phagocytic activity. Experiments using agonists and antagonists indicated that serotonin 5-hydroxytryptamine (5-HT) induced the alteration of their phenotype and reduction in antigen-presenting capacity were mediated via 5-HTR1/7. It is therefore suggested that serotonin-driven DC may have a regulatory function in the inflammatory process.

Summary LIGHT [the name of which is derived from ‘homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes’], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP‐1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP‐1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin‐1β in THP‐1 cells. Apoptosis was inhibited, the Bcl‐2 level increased and the caspase‐3 level decreased in THP‐1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.

Congenital malignant melanoma (MM) is an uncommon condition that is defined as MM recognized at birth. Its incidence is difficult to determine because of the small number of reported cases and because of problems associated with diagnosis. Generally, Spitz naevus and melanoma have many clinical and histopathological similarities, so it is difficult to differentiate between the two. We describe a rare case of congenital MM in which differential diagnosis from Spitz naevus was problematic. In addition, we review the literature and comment on the prognostic differences among the three types of congenital and infantile MM.

The local cytokine environment and the presence of stimulatory signals determine whether monocytes acquire dendritic cell or macrophage characteristics and functions. In this study, we examined the effect of histamine, a prototypic mediator of allergic inflammation, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived dendritic cells (MoDC), which typically showed CD1a+CD14- phenotype. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of histamine, and the phenotypes and function of these cells were analyzed. Histamine induced the generation of CD1a-CD14+ cells, which exhibited cytological and phenotypical characteristics of dendritic cells (DC), showed enhanced phagocytic activity and cytokine-producing capacity, but demonstrated weak allo-stimulatory capacity compared with CD1a+CD14- MoDC. The inhibitory effects of histamine on CD1a+CD14- MoDC differentiation were antagonized by cimetidine, an H2 receptor antagonist, but not by H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. Culture supernatant of histamine-treated monocytes also inhibited CD1a+CD14- MoDC differentiation, which was restored by the removal of IL-10. These results suggest that histamine-driven CD1a-CD14+ DC amplify their antigen-independent inflammatory reaction and may contribute to the exacerbation of allergic diseases.

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Summary Contact hypersensitivity (CHS) is a T-cell-mediated skin inflammatory response. It is controversial whether CD4+ Keywords: contact hypersensitivity, hapten, IL-16, keratinocytes I ntroductionContact hypersensitivity (CHS) is a T cell-mediated immune reaction that occurs after epicutaneous sensitization and challenge with reactive haptens [1,2] The nature of the cell type involved in hapten presentation to specific T cells during the elicitation phase of CHS remains to be determined. Interleukin (IL)-16 was described originally as a lymphocyte chemoattractant factor that is generated from mitogenor antigen-stimulated human peripheral blood mononuclear cells [6]. Subsequent studies found that IL-16 is produced by lymphocytes, mast cells, dendritic cells, epithelial cells, fibroblasts and eosinophils [7][8][9] and induces chemotaxis via direct interaction with CD4 molecule as its natural ligand in CD4-expressing cells such as T cells, eosinophils, mast cells, dendritic cells and monocytes [8,10,11]. In addition to being a chemoattractant factor, several immunomodulatory functions of IL-16 have been identified. IL-16 stimulates cytokine production in monocytes and upregulates their expression of co-stimulatory molecules and MHC class II molecules [12,13]. In contrast, it reduces proliferative responses and IL-2 production in CD4 + T cells [14,15]. Although IL-16 was reported to play a role in DTH by chemoattracting CD4 + T cells [16], no information is available on the expression and role of IL-16 in CHS.In the present study, we show that IL-16 is produced by epidermal cells, especially keratinocytes, and dermal cells during the sensitization and elicitation phases of hapten-induced CHS. We also show that treatment of sensitized mice with neutralizing monoclonal antibody against IL-16 before hapten challenge significantly suppresses the CHS response, suggesting that IL-16 plays a regulatory role in the elicitation phase. Materials and methods AnimalsMale and female BALB/c mice, female C57BL6 mice and C3H/HeN mice aged 6-8 weeks were purchased from

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