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Dendritic cell (DC) immunotherapy is a strong candidate for the treatment of incurable cancers especially malignant melanoma. Nevertheless, the proper guideline of DC immunotherapy does not exist. The absence of the guideline is also an obstacle to clinical trials of DC immunotherapy. So we conducted this study in order to develop an effective DC preparation method for immunotherapy in mouse malignant melanoma. Mouse bone marrow-derived DC were stimulated with tumour antigen alone or tumour antigen plus a cocktail (anti-CD40 antibody +TNF-alpha+ IL-1beta) for 8, 24 or 48 h and the characteristics of these DC, such as surface molecules (CD40, CD80, CD86, MHC class II, CCR7), cytokines(IL-12, IFN-gamma, and IL-10), DC-induced T cell proliferation in vitro, and the production of IFN-gamma by those cells, were evaluated. Mice with melanoma were then treated with DC stimulated with tumour antigen alone and tumour antigen plus cocktail for 8 or 48 h. The tumour size and survival rate of these mice were then evaluated. (1) Beneficial clinical effects such as a reduction of tumour size and an increased survival rate were best observed in the group treated with DC stimulated for 8 h with tumour antigen plus cocktail. (2) The single prominent characteristic of DC stimulated for 8 h with tumour antigen plus cocktail was an elevated IL-12 secretion. The cytokine IL-12 was not secreted by other DC. Consequently, proper production of IL-12 was found to be an important requirement for DC used in immunotherapy of mouse melanoma.

ROS are produced in dendritic cells (DCs) during antigen presentation in contact hypersensitivity (CHS). As a result, ROS cause a number of nonenzymatic protein modifications, including carbonylation, which is the most widely used marker of oxidative stress. 2,4,6-Trinitrobenzene sulfonic acid (TNBS) is a well-characterized contact allergen that results in the formation of ROS. However, proteins that are carbonylated in DCs in response to TNBS have not been identified. To study ROS-dependent protein carbonylation in response to TNBS, we used the well-established mouse DC line, XS-106. We focused on the effects of TNBS on oxidation by examining selected oxidative markers. We identified TNBS-induced ROS and myeloperoxidase (MPO) proteins and demonstrated that the increase in ROS resulted in IL-12 production. The increase in oxidation was further confirmed by an oxidation-dependent increase in protein modifications, such as carbonylation. In fact, TNBS strongly induced carbonylation of mitochondrial adenosine triphosphate (ATP) synthase in XS-106 DCs, as determined by MALDI-TOF analysis and 2-D Western blotting. ROS production and protein carbonylation were confirmed in human monocyte-derived DCs (Mo-DCs). Furthermore, glutathione (GSH) decreased ROS and protein carbonylation in Mo-DCs. Carbonylation of ATP synthase in DCs may contribute to the pathophysiology of CHS.

Hypertrichosis lanuginosa acquisita (HLA) is an unusual condition which is characterized by subtle and progressive development of multiple, long, thin, unmedullated hairs ("lanugo hairs") distributed preferentially on the face. Most cases are associated with malignant tumors or non-malignant condition such as porphyria cutanea tarda, AIDS, anorexia nervosa, thyrotoxicosis, or secondary to topical or systemic drugs (e.g. cyclosporine, phenytoin, diazoxide, minoxidil). We have recently experienced a rare case of hypertrichosis lanuginosa acquisita associated with autoimmune hepatitis. To our best knowledge, this is the first report of hypertrichosis lanuginosa acquisita associated with autoimmune hepatitis. Our observation expands the spectrum of diseases associated with this uncommon disorder.