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( Dashlkhumbe Byamba ),( Tae Gyun Kim ),( Dong Hyun Kim ),( Jeong Hwan Je ),( Min Geol Lee ) 대한피부과학회 2010 Annals of Dermatology Vol.22 No.3
Background: Although reactive oxygen species (ROS) have been produced in both mouse bone marrow-derived dendritic cells (DCs) and XS-106 DCs by contact sensitizers and irritants in previous studies, the generation of ROS in human monocyte-derived DCs (MoDCs) and their role in contact hypersensitivity (CHS) has yet to be elucidated. Objective: The purpose of this study was to determine whether contact allergens and irritants induce ROS in MoDCs and, if so, to evaluate the role of contact allergen and irritant induced-ROS in MoDCs in CHS. Methods: Production of ROS was measured by 5-(and-6)-chloromethyl-2`,7`-dichlorodihydrofluorescein diacetate (CM-H2DCFDA) assay. Surface CD86 and HLA-DR molecules were detected by flow cytometry. Protein carbonylation was detected by Western blotting. Results: ROS were produced by contact allergens such as dinitrochlorobenzene (DNCB) and thimerosal and the irritant benzalkonium chloride (BKC). DNCB-induced, but not BKC-induced, ROS increased surface CD86 and HLA-DR molecules on MoDCs and induced protein carbonylation. These changes were reduced in the presence of antioxidant N-acetyl cysteine. Conclusion: Our results suggest that DNCB-induced ROS may be different from those induced by irritant BKC. The DNCB-induced ROS may be associated with the CHSresponse, because they activate surface molecules on DCs that are important for generating immune reactions. (Ann Dermatol 22(3) 269∼278, 2010)
김대석,이민걸,김동현,구본철,조영훈,박진모,이태형,김현옥,김한수,이현아,이종두,Dashlkhumbe Byamba,제정환 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.6
Purpose: Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea. Materials and Methods: Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10^7 DC were injected each time. Results: Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients. Conclusion: In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.
다양한 Haptens 및 자극물질에 의한 마우스 골수 수지상세포의 활성산소종의 생성과 역할
김대석 ( Dae Suk Kim ),김동현 ( Dong Hyun Kim ),이태형 ( Tae Hyung Lee ),조영훈 ( Young Hun Cho ),이민걸 ( Min Geol Lee ),( Dashlkhumbe Byamba ) 대한피부과학회 2008 대한피부과학회지 Vol.46 No.11
Background: Various allergens and irritants induced the production of reactive oxygen species (ROS) in the well-established mouse dendritic cell (DC) line XS106 and this production of ROS was inhibited by antioxidants. Objective: To investigate the production and functions of ROS in mouse bone marrow-derived DCs (BM-DCs) by various haptens and irritants, we examined the production of ROS, the expression of surface molecules, and the production of interleukin-12 (IL-12) in mouse BM-DCs. Methods: Six to eight-week-old female C57/BL6 mice were used in this study. Mouse BM-DCs were co-cultured with DNFB, DNCB, TNBS, hydroquinone, NiSO4, CoCl2, MnCl2, thimerosal, SDS, and BKC. The production of ROS and the expression of surface molecules (CD40, CD80, CD86, and MHC-II) were measured by flow cytometry in chemical-treated mouse BM-DCs. In addition, the cells were pretreated with antioxidants to determine whether the production of ROS can be inhibited. The production of IL-12 was also measured in DNCB and SDS-treated mouse BM-DCs using ELISA. Results: The production of ROS in mouse BM-DCs was induced by various allergens, including DNFB, DNCB, TNBS, hydroquinone, MnCl2 and irritants like SDS, BKC. The expression of surface molecules was induced by various chemicals and NiSO4 was the most potent inducer of surface molecules in mouse BM-DCs. The production of ROS in DNCB and SDS-treated mouse BM-DCs was partially inhibited by diphenylene iodonium, but not by rotenone, vitamin E, allopurinol, glutathione. The production of IL-12 was not detected in DNCB and SDS-treated mouse BM-DCs. Conclusion: The production of ROS was induced in mouse BM-DCs by various allergens and irritants. The expression of surface molecules was also induced by various chemicals. The production of ROS was partially inhibited by DPI. The production of IL-12 was not detected. (Korean J Dermatol 2008; 46 (11): 1470∼1477)