ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1841

BAFF Induces Production of Matrix Metalloproteinase-9 By Peripheral Monocytes in Patients With Primary Sjögren’s Syndrome Through a Signaling Pathway That Involves NF-Kb and PI3 Kinase

Keiko Yoshimoto1, Maiko Tanaka2, Masako Kojima2, Hideko Ogata2, Eriko Ishioka3, Ayumi Nishikawa2, Katsuya Suzuki1, Hideto Kameda1, Tohru Abe4 and Tsutomu Takeuchi5, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 3Division of Rheumatology, Department of Internal medicine, Keio University School of Medicine, Tokyo, Japan, 4Dept Int Med Saitama Med Ctr, Saitama Medical School, Kawagoe-shi Saitama, Japan, 5Keio University School of Medicine, Tokyo, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis II

Session Type: Abstract Submissions (ACR)

Background/Purpose: B cell activating factor of the TNF family (BAFF) regulates proliferation, differentiation and survival of B cells, and plays a pivotal role in the development of primary Sjögren’s syndrome (pSS). In our previous study, we found that IL-6 production was significantly enhanced in pSS monocytes upon stimulation with BAFF. We also found that the expression level of a BAFF receptor (BAFF-R) was significantly elevated in pSS monocytes compared to that of normal monocytes. These data collectively suggest that the elevated expression of BAFF-R on monocytes is involved in activation of monocytes to promote IL-6 production. Matrix metalloproteinase-9 (MMP-9) is one of the enzymes involved in pathogenesis of autoimmune diseases. In this study, we explored possible involvement of BAFF and BAFF-R in the expression of MMP-9 in pSS monocytes.

Methods: The expression levels of BAFF-R and MMP-9 in peripheral monocytes of pSS patients (n = 19) and age matched normal individuals (n = 14) were analyzed by FACS. The cells were cultured in vitro in the presence or absence of recombinant human soluble BAFF (rhsBAFF) for 96 hrs, and the amounts of IL-6 and MMP-9 in the culture supernatants were measured by ELISA. The expression level of MMP-9 was also analyzed by quantitative PCR. Signal transduction pathways were investigated by exposing rhsBAFF-stimulated pSS monocytes to several inhibitors against NF-κB (BAY11-7082 and BAY11-7085) and PI3 kinase (LY294002).

Results: Quantitative PCR and FACS analyses revealed that stimulation of pSS moncytes with rhsBAFF drastically enhanced the expression of MMP-9 compared to that of normal monocytes. ELISA showed robust enhancement of MMP-9 production by pSS monocytes. Remarkably, the amount of MMP-9 was positively correlated with the expression level of BAFF-R on pSS monocytes, suggesting that BAFF-signaling is involved in the production of MMP-9 by pSS monocytes. Moreover, the elevated production of MMP-9 was significantly suppressed by specific inhibitors against NF-κB and PI3 kinase in a dose dependent manner.

Conclusion: The present study suggests that the BAFF signaling pathway is involved in the production of MMP-9 by pSS monocytes. The study also suggests that NF-κB and PI3 kinase are involved in the pathway.

Disclosure:

K. Yoshimoto,
None;

M. Tanaka,
None;

M. Kojima,
None;

H. Ogata,
None;

E. Ishioka,
None;

A. Nishikawa,
None;

K. Suzuki,
None;

H. Kameda,
None;

T. Abe,
None;

T. Takeuchi,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/baff-induces-production-of-matrix-metalloproteinase-9-by-peripheral-monocytes-in-patients-with-primary-sjogrens-syndrome-through-a-signaling-pathway-that-involves-nf-kb-and-pi3-kinase/