Senda Naoyuki, Miyagaki Tomomitsu, Kamijo Hiroaki, Nakajima Rina, Oka Tomonori, Takahashi Naomi, Suga Hiraku, Yoshizaki Ayumi, Asano Yoshihide, Sugaya Makoto, Sato Shinichi
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan, Department of Dermatology, International University of Health and Welfare Faculty of Medicine, Chiba, Japan.
Eur J Dermatol. 2018 Oct 1;28(5):621-627. doi: 10.1684/ejd.2018.3400.
High mobility group box-1 (HMGB1) is a ubiquitously expressed non-histone nuclear protein which acts as a danger signal when released from cells. HMGB1, which is associated with inflammation, angiogenesis, and T helper (Th)2 polarization, contributes to the development of various inflammatory diseases and malignancies. However, it remains to be determined whether HMGB1 is involved in cutaneous T-cell lymphoma (CTCL).
To investigate the role of HMGB1 in CTCL.
MATERIALS & METHODS: Serum HMGB1 levels were measured in patients with CTCL and healthy controls using an enzyme-linked immunosorbent assay. HMGB1 messenger RNA (mRNA) expression in CTCL and normal skin was examined by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Moreover, we analysed correlations between the levels of HMGB1 and other cytokines and chemokines, laboratory data, disease activity, and prognosis.
HMGB1 levels were significantly higher in sera of CTCL patients than those of normal controls and correlated with serum levels of soluble interleukin-2 receptor, lactate dehydrogenase, thymus and activation-regulated chemokine, and the number of eosinophils in peripheral blood. Serum HMGB1 levels also reflected disease activity and prognosis for each patient with CTCL. HMGB1 mRNA levels in CTCL lesional skin were significantly elevated and correlated with IL-4, IL-10, IL-19, and angiogenin mRNA levels. Immunohistochemical staining revealed that HMGB1 was expressed not only in the nucleus but also in the cytoplasm of various cells in CTCL lesional skin.
These results suggest that enhanced HMGB1 expression may contribute to the progression of CTCL through Th2 polarization and promotion of angiogenesis.
高迁移率族蛋白B1（HMGB1）是一种广泛表达的非组蛋白核蛋白，当从细胞中释放时作为一种危险信号。HMGB1与炎症、血管生成和辅助性T细胞（Th）2极化相关，促成各种炎症性疾病和恶性肿瘤的发展。然而，HMGB1是否参与皮肤T细胞淋巴瘤（CTCL）仍有待确定。
研究HMGB1在CTCL中的作用。
采用酶联免疫吸附测定法测量CTCL患者和健康对照者血清中HMGB1水平。通过定量逆转录聚合酶链反应和免疫组织化学检测CTCL和正常皮肤中HMGB1信使核糖核酸（mRNA）表达。此外，我们分析了HMGB1水平与其他细胞因子和趋化因子、实验室数据、疾病活动度及预后之间的相关性。
CTCL患者血清中HMGB1水平显著高于正常对照者，且与可溶性白细胞介素-2受体、乳酸脱氢酶、胸腺和活化调节趋化因子的血清水平以及外周血嗜酸性粒细胞数量相关。血清HMGB1水平还反映了每位CTCL患者的疾病活动度和预后。CTCL皮损中HMGB1 mRNA水平显著升高，并与白细胞介素-4、白细胞介素-10、白细胞介素-19和血管生成素mRNA水平相关。免疫组织化学染色显示，HMGB1不仅在CTCL皮损中各种细胞的细胞核中表达，也在细胞质中表达。
这些结果表明，HMGB1表达增强可能通过Th2极化和促进血管生成促成CTCL的进展。
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