Barkauskaite V, Ek M, Popovic K, Harris H E, Wahren-Herlenius M, Nyberg F
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Lupus. 2007;16(10):794-802. doi: 10.1177/0961203307081895.
HMGB1 is a pro-inflammatory cytokine that together with TNF-alpha and IL-1beta 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-1beta 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-1beta was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1beta was seen predominantly in late biopsies.In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced 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-1beta, and formation of a pro-inflammatory loop between HMGB1, TNF-alpha, and IL-1beta may be responsible for the prolonged and sustained inflammation in CLE.
高迁移率族蛋白B1（HMGB1）是一种促炎细胞因子，它与肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）共同参与红斑狼疮自发皮肤病变的发病机制。本研究的目的是探讨在实验性诱导的皮肤红斑狼疮（CLE）病变发展和消退过程中，HMGB1、TNF-α和IL-1β表达的事件顺序。该研究包括对9例CLE患者光激发皮肤病变获取的38份连续皮肤活检样本进行组织切片免疫组化染色。与病变后期、消退期或非病变皮肤相比，在皮肤受累临床最活跃期的活检样本中发现了细胞外分泌的HMGB1和细胞质中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，这些细胞因子并非在所有病变中都上调，且IL-1β表达增加主要见于后期活检样本。总之，细胞外和细胞质中的HMGB1与皮肤狼疮光诱导病变的临床最活跃期一致，提示HMGB1是CLE炎症性自身免疫过程中的一个重要因素。HMGB1可诱导TNF-α和IL-1β表达，HMGB1、TNF-α和IL-1β之间促炎环路的形成可能是CLE中炎症持续存在的原因。
