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: matrix metalloproteinase (MMP)

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/