Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren's syndrome

Keiko Yoshimoto, Maiko Tanaka, Masako Kojima, Yumiko Setoyama, Hideto Kameda, Katsuya Suzuki, Kensei Tsuzaka, Yoko Ogawa, Kazuo Tsubota, Tohru Abe, Tsutomu Takeuchi

Research output: Contribution to journalArticle

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Abstract

Introduction: In this study, we investigated possible aberrations of monocytes from patients with primary Sjogren's syndrome (pSS). We focused on BAFF (B cell activating factor of the TNF family) and IL-6, because they are both produced by monocytes and 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-gamma, and the amounts of IL-6 and 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 compared to normal monocytes, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-gamma. 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 present study suggests that the mechanisms for the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is ascribed to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may underlie the development of pSS.

Original languageEnglish
JournalArthritis research & therapy
DOIs
Publication statusAccepted/In press - 2011 Oct 21

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Sjogren's Syndrome
Monocytes
Interleukin-6
B-Cell Activation Factor Receptor
Transcription Factors
B-Cell Activating Factor
Anti-Idiotypic Antibodies
Cytokines
Gene Expression

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Rheumatology
  • Medicine(all)

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Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren's syndrome. / Yoshimoto, Keiko; Tanaka, Maiko; Kojima, Masako; Setoyama, Yumiko; Kameda, Hideto; Suzuki, Katsuya; Tsuzaka, Kensei; Ogawa, Yoko; Tsubota, Kazuo; Abe, Tohru; Takeuchi, Tsutomu.

In: Arthritis research & therapy, 21.10.2011.

Research output: Contribution to journalArticle

Yoshimoto, Keiko ; Tanaka, Maiko ; Kojima, Masako ; Setoyama, Yumiko ; Kameda, Hideto ; Suzuki, Katsuya ; Tsuzaka, Kensei ; Ogawa, Yoko ; Tsubota, Kazuo ; Abe, Tohru ; Takeuchi, Tsutomu. / Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjogren's syndrome. In: Arthritis research & therapy. 2011.
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AU - Kojima, Masako

AU - Setoyama, Yumiko

AU - Kameda, Hideto

AU - Suzuki, Katsuya

AU - Tsuzaka, Kensei

AU - Ogawa, Yoko

AU - Tsubota, Kazuo

AU - Abe, Tohru

AU - Takeuchi, Tsutomu

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N2 - Introduction: In this study, we investigated possible aberrations of monocytes from patients with primary Sjogren's syndrome (pSS). We focused on BAFF (B cell activating factor of the TNF family) and IL-6, because they are both produced by monocytes and 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-gamma, and the amounts of IL-6 and 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 compared to normal monocytes, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-gamma. 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 present study suggests that the mechanisms for the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is ascribed to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may underlie the development of pSS.

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