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Nothofagin suppresses mast cell-mediated allergic inflammation
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-10-28 , DOI: 10.1016/j.cbi.2018.10.025
Byeong-Cheol Kang , Min-Jong Kim , Soyoung Lee , Young-Ae Choi , Pil-Hoon Park , Tae-Yong Shin , Taeg Kyu Kwon , Dongwoo Khang , Sang-Hyun Kim

Mast cells play a major role in immunoglobulin E-mediated allergic inflammation, which is involved in asthma, atopic dermatitis, and allergic rhinitis. Nothofagin has been shown to ameliorate various inflammatory responses such as the septic response and vascular inflammation. In this study, we assessed the inhibitory effect of nothofagin on allergic inflammation using cultured/isolated mast cells and an anaphylaxis mouse model. Nothofagin treatment prevented histamine and β-hexosaminidase release by reducing the influx of calcium into the cytosol in a concentration-dependent manner. Nothofagin also inhibited the gene expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-4 by downregulating the phosphorylation of Lyn, Syk, Akt and nuclear translocation of nuclear factor-κB. To confirm these effects of nothofagin in vivo, we used a passive cutaneous anaphylaxis mouse model. Topical administration of nothofagin suppressed local pigmentation and ear thickness. Taken together, these results suggest nothofagin as a potential candidate for the treatment of mast cell-involved allergic inflammatory diseases.



中文翻译:

Nothofagin抑制肥大细胞介导的过敏性炎症

肥大细胞在免疫球蛋白E介导的变态反应性炎症中起主要作用,其与哮喘,特应性皮炎和变应性鼻炎有关。已显示Nothofagin可改善各种炎症反应,例如脓毒症反应和血管炎症。在这项研究中,我们使用培养的/分离的肥大细胞和过敏性小鼠模型评估了诺夫沙汀对过敏性炎症的抑制作用。Nothofagin处理通过以浓度依赖的方式减少钙向细胞质中的流入,从而阻止了组胺和β-己糖胺酶的释放。Nothofagin还通过下调Lyn,Syk,Akt的磷酸化和核因子-κB的核转运来抑制促炎性细胞因子(如肿瘤坏死因子-α和白介素-4)的基因表达和分泌。在体内,我们使用了被动皮肤过敏反应小鼠模型。Nothofagin的局部给药可抑制局部色素沉着和耳朵厚度。综上所述,这些结果表明,诺霍芬汀是治疗肥大细胞相关的变应性炎症疾病的潜在候选者。

更新日期:2018-10-28
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