Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 301-746, Republic of Korea.
Life Sci. 2012 Sep 24;91(9-10):338-44. doi: 10.1016/j.lfs.2012.07.021. Epub 2012 Jul 31.
In this study, we synthesized a novel chemical, (E)-2-(3,4-dimethoxyphenyl)-4-oxo-4H-chromen-7-yl-3-(3,4-dimethoxyphenyl) acrylate (CSH) and investigated the effect of CSH on atopic dermatitis (AD) by evaluating the anti-inflammatory effect of CSH on immune cells in vitro and on atopic dermatitis-like lesions in vivo.
Human monocytic THP-1 cells and human eosinophilic EoL-1 cells were treated with house dust mite extract in the absence and presence of CSH. Nc/Nga mice were sensitized to 2,4-dinitrochlorobenzne (DNCB) for 5 weeks and then orally and dorsally administered with CSH or dexamethasone for 3 weeks.
CSH inhibited the secretion of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6 and IL-8 due to house dust mite extract in THP-1 cells. CSH also suppressed the secretion of MCP-1 and IL-8 in EoL-1 cells. In vivo, the skin severity score decreased after CSH treatment as compared to the control group. CSH suppressed the inflammatory cell infiltration into the dermis and thickened the epidermis. CSH reduced serum IgE level as compared to the control group. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A and the increase of the cytokines was decreased by pre-treatment with CSH. The inhibitory effects of CSH on atopic lesions of DNCB-treated Nc/Nga mice were similar to those of dexamethasone, despite differing degrees depending on results evaluated in this study.
These results may contribute to the development of a therapeutic drug for the treatment of AD.
本研究合成了一种新型化合物（E）-2-（3,4-二甲氧基苯基）-4-氧代-4H-色烯-7-基-3-（3,4-二甲氧基苯基）丙烯酰胺（CSH），并通过评估 CSH 对体外免疫细胞和体内特应性皮炎样病变的抗炎作用，研究 CSH 对特应性皮炎（AD）的影响。
用屋尘螨提取物处理人单核细胞 THP-1 细胞和人嗜酸性粒细胞 EoL-1 细胞，同时存在和不存在 CSH。Nc/Nga 小鼠用 2,4-二硝基氯苯（DNCB）致敏 5 周，然后用 CSH 或地塞米松口服和背部给药 3 周。
CSH 抑制了 THP-1 细胞中屋尘螨提取物引起的单核细胞趋化蛋白-1（MCP-1）、白细胞介素（IL）-6 和 IL-8 的分泌。CSH 还抑制了 EoL-1 细胞中 MCP-1 和 IL-8 的分泌。在体内，与对照组相比，CSH 治疗后皮肤严重程度评分降低。CSH 抑制了真皮炎症细胞浸润和表皮增厚。与对照组相比，CSH 降低了血清 IgE 水平。与 ConA 处理相比，CSH 预处理可降低小鼠脾细胞中 IL-4、IL-5、IL-13 和 eotaxin 的水平。
这些结果可能有助于开发治疗 AD 的治疗药物。
