Increased extracellular levels of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in minor salivary glands of patients with Sjögren's syndrome.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ek
Monica
M
Rheumatology Unit, Center for Molecular Medicine L8:04, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Popovic
Karin
K
Harris
Helena Erlandsson
HE
Nauclér
Cecilia Söderberg
CS
Wahren-Herlenius
Marie
M
D001706:Biopsy; D016022:Case-Control Studies; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D024243:HMGB1 Protein; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha