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

Arthritis Res Ther. 2011;13(5):R170. doi: 10.1186/ar3493. Epub 2011 Oct 21.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Cell Activating Factor / antagonists & inhibitors
  • B-Cell Activating Factor / biosynthesis*
  • B-Cell Activating Factor / metabolism
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / biosynthesis*
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Sjogren's Syndrome / metabolism*
  • Sjogren's Syndrome / pathology*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • B-Cell Activating Factor
  • Interleukin-6
  • TNFSF13B protein, human
  • Transcription Factors