Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjögren's syndrome.
BACKGROUND
In this study, we investigated possible aberrations of monocytes from patients with primary Sjögren's syndrome (pSS). We focused on B-cell-activating factor of the TNF family (BAFF) and IL-6 because they are both produced by monocytes and are known to be involved in the pathogenesis of pSS.


METHODS
Peripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-γ, and the amounts of IL-6 and soluble BAFF (sBAFF) produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated.


RESULTS
Peripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 than normal monocytes did, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-γ. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes.


CONCLUSIONS
The results of the present study suggest that the mechanisms underlying the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is due to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may cause the development of pSS.
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. keikoy@a8.keio.jp
Keiko
K
Yoshimoto
Maiko
M
Tanaka
Masako
M
Kojima
Yumiko
Y
Setoyama
Hideto
H
Kameda
Katsuya
K
Suzuki
Kensei
K
Tsuzaka
Yoko
Y
Ogawa
Kazuo
K
Tsubota
Tohru
T
Abe
Tsutomu
T
Takeuchi
D000328:Adult; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
D053264:B-Cell Activating Factor; D015850:Interleukin-6; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors; C505719:TNFSF13B protein, human