Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus
Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus
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DOI：
10.1177/0961203307081895
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发表时间：
2007-01-01
期刊：
影响因子：
2.6
通讯作者：
Nyberg, F.
中科院分区：
文献类型：
--
作者：
Barkauskaite, V.;Ek, M.;Nyberg, F.
HMGB1 是一种促炎细胞因子，与 TNF-α 和 IL-1β 一起参与红斑狼疮自发性皮肤病变的发病机制。本研究的目的是探讨实验诱导的 CLE 病变发展和消退过程中 HMGB1、TNF-α 和 IL-1β 表达的事件顺序。该研究使用组织切片的免疫组织化学染色技术，对从 9 名 CLE 患者的光诱发皮肤病变中采集的 38 份连续皮肤活检进行了调查。在皮肤受累临床最活跃阶段的活检中，与晚期和褪色病变或非病变皮肤相比，发现细胞外分泌的 HMGB1 和细胞质 HMGB1 增加。除 HMGB1 外，在诱导的 CLE 病变的真皮浸润中还观察到 TNF-α 和 IL-1β 表达增加。然而，这些细胞因子并未在所有病变中上调，并且主要在晚期活检中观察到 IL-1β 表达增加。 总之。细胞外和细胞质HMGB1与皮肤狼疮光内病变临床最活跃期相一致，提示HMGB1是CLE炎症自身免疫过程的重要因素。 HMGB1可以诱导TNF-α和IL-1β的表达，HMGB1、TNF-α和IL-1β之间促炎环的形成可能是CLE中长期持续炎症的原因。
HMGB1 is a pro-inflammatory cytokine that together with TNF-alpha and IL-1 beta is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-alpha and IL-1 beta expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-alpha and IL-1 beta was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1 beta was seen predominantly in late biopsies.In conclusion. extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoincluced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-alpha and IL-1 beta, and formation of a pro-inflammatory loop between HMGB1, TNF-alpha, and IL-1 beta may be responsible for the prolonged and sustained inflammation in CLE.