DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts
DHMEQ, a novel NF-kappaB inhibitor, suppresses growth and type I collagen accumulation in keloid fibroblasts
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DOI：
10.1016/j.jdermsci.2008.03.003
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Yamashita, Shunichi
中科院分区：
文献类型：
--
作者：
Makino, Sachio;Mitsutake, Norisato;Yamashita, Shunichi
背景：瘢痕疙瘩是一种皮肤良性肿瘤，以成纤维细胞增殖和细胞外基质（ECM）过度分泌为特征。核因子-κ B（NF-κ B）在炎症、免疫应答和细胞增殖的调节中起重要作用。NF-κ B通路的激活被认为与瘢痕疙瘩成纤维细胞的异常增殖和ECM的产生密切相关。目的：本研究旨在探讨一种新型的选择性NF-κ B抑制剂去羟甲基表氧喹诺霉素（DHMEQ）对瘢痕疙瘩成纤维细胞的作用。方法：采用原代正常和瘢痕疙瘩真皮成纤维细胞进行实验。NF-κ B B活性用DNA结合法和免疫组化法检测。DHMEQ的效果进行了评估，细胞活力，细胞生长和I型胶原accumulation.Results：基础NF-κ B活性组成性升高，在瘢痕疙瘩成纤维细胞，表明这一途径参与瘢痕疙瘩的发病机制。结论：DHMEQ抑制NF-κ B B表达可能是治疗瘢痕疙瘩的一种有效方法。(c)2008年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Keloid is a benign dermal tumor characterized by proliferation of dermal fibroblasts and overproduction of extracellular matrix (ECM). Nuclear factor kappaB (NF-kappa B) plays an important role in regulation of inflammation, immune response and cell proliferation. Activation of the NF-kappa B pathway is thought to be closely linked to abnormal cell proliferation and ECM production in keloid fibroblasts.Objective: This study was set out to investigate the effects of a novel selective NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on keloid fibroblasts. Methods: Primary normal and keloid dermal fibroblasts were used for this study. NF-kappa B activity was assessed by DNA-binding assay and immunohistochemistry. The effect of DHMEQ was evaluated by cell viability, cell growth and type I collagen accumulation.Results: Basal NF-kappa B activity was constitutively elevated in keloid fibroblasts, indicating that this pathway is involved in keloid pathogenesis. DHMEQ markedly reduced cell proliferation and type I collagen accumulation in keloid fibroblasts.Conclusion: The inhibition of NF-kappa B by DHMEQ may be an attractive therapeutic approach for keloids. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.