Ek Monica, Popovic Karin, Harris Helena Erlandsson, Nauclér Cecilia Söderberg, Wahren-Herlenius Marie
Rheumatology Unit, Center for Molecular Medicine L8:04, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Arthritis Rheum. 2006 Jul;54(7):2289-94. doi: 10.1002/art.21969.
To investigate the expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 (HMGB-1) in the salivary glands of patients with Sjögren's syndrome (SS) and patients with sicca symptoms.
Biopsy samples from the minor labial salivary glands of patients with SS, patients with sicca symptoms but no diagnosis of SS, and healthy controls were investigated. Expression of HMGB-1, tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) was analyzed using immunohistochemical staining on consecutive cryosections.
Increased expression of HMGB-1 was observed among the large infiltrates of mononuclear cells found in biopsy samples from patients with SS, and the degree of extracellular HMGB-1 was significantly higher in patients with SS compared with patients with sicca symptoms and with healthy controls (P < 0.05 and P < 0.01, respectively). Cellular expression of TNF was increased in patients with SS and in patients with sicca symptoms. In addition, the level of secreted TNF was significantly higher in patients with SS than in healthy controls (P < 0.05). Intracellular expression of IL-1beta was detected in all groups, while extracellular IL-1beta was observed almost exclusively among the infiltrating mononuclear cells of patients with SS.
The increased amount of extracellular HMGB-1 observed in salivary glands of patients with SS indicates that HMGB-1 is involved in the inflammatory process of the disease. This cytokine, along with TNF and IL-1beta, may form a proinflammatory loop that promotes the chronic features of the glandular inflammation in SS.
研究新型促炎细胞因子高迁移率族蛋白B1(HMGB - 1)在干燥综合征(SS)患者及有口干症状患者唾液腺中的表达情况。
对SS患者、有口干症状但未诊断为SS的患者以及健康对照者的下唇小唾液腺活检样本进行研究。在连续的冰冻切片上采用免疫组织化学染色分析HMGB - 1、肿瘤坏死因子(TNF)和白细胞介素 - 1β(IL - 1β)的表达。
在SS患者活检样本中发现的大量单核细胞浸润中观察到HMGB - 1表达增加,与有口干症状患者及健康对照者相比,SS患者细胞外HMGB - 1水平显著更高(分别为P < 0.05和P < 0.01)。SS患者及有口干症状患者中TNF的细胞表达增加。此外,SS患者分泌的TNF水平显著高于健康对照者(P < 0.05)。所有组均检测到IL - 1β的细胞内表达,而细胞外IL - 1β几乎仅在SS患者的浸润单核细胞中观察到。
在SS患者唾液腺中观察到的细胞外HMGB - 1量增加表明HMGB - 1参与了该疾病的炎症过程。这种细胞因子与TNF和IL - 1β一起可能形成一个促炎循环,促进SS中腺体炎症的慢性特征。