Open Access Research article

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

Keiko Yoshimoto1*, Maiko Tanaka1, Masako Kojima1, Yumiko Setoyama2, Hideto Kameda1, Katsuya Suzuki2, Kensei Tsuzaka3, Yoko Ogawa4, Kazuo Tsubota4, Tohru Abe2 and Tsutomu Takeuchi1

Author affiliations

1 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan

2 Division of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamodatsujido-cho, Kawagoe, Saitama 350-8550, Japan

3 Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital, 5-11-3 Sugano, Ichikawa, Chiba 272-8513, Japan

4 Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan

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Citation and License

Arthritis Research & Therapy 2011, 13:R170  doi:10.1186/ar3493

Published: 21 October 2011

Abstract

Introduction

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.