International Immunology, Vol. 12, No. 2, 187-193,
February 2000
© 2000 Japanese Society for Immunology
IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor
Department of Medical Science I, School of Health and Sport Sciences, Osaka University, 2-1 Yamadaoka, Suita-city, Osaka 565-0871, Japan
1 Department of Orthopedics, Osaka University Medical School, Osaka 565-0871, Japan
Correspondence to: K. Yoshizaki
IL-6 and tumor necrosis factor (TNF)-
have been proven to play an important role in the development of rheumatoid arthritis (RA). It is well known that TNF- induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitrostudy was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF- increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6–sIL-6R complex reduced the TNF--induced proliferation of synovial cells while TNF- induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF--induced synovial cell growth.
Keywords: IL-6, rheumatoid arthritis, soluble IL-6 receptor, synovial cell, tumor necrosis factor-
Transmitting editor: K. Okumura
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. NONOMURA, F. MIZOGUCHI, A. SUZUKI, T. NANKI, H. KATO, N. MIYASAKA, and H. KOHSAKA Hypoxia-induced Abrogation of Contact-dependent Inhibition of Rheumatoid Arthritis Synovial Fibroblast Proliferation J Rheumatol, April 1, 2009; 36(4): 698 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nishimoto, Y. Kanakura, K. Aozasa, T. Johkoh, M. Nakamura, S. Nakano, N. Nakano, Y. Ikeda, T. Sasaki, K. Nishioka, et al. Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease Blood, October 15, 2005; 106(8): 2627 - 2632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Nakanishi, K. Yoshioka, S. Joyama, N. Araki, A. Myoui, S. Ishiguro, T. Ueda, H. Yoshikawa, and K. Itoh Interleukin-6/Soluble Interleukin-6 Receptor Signaling Attenuates Proliferation and Invasion, and Induces Morphological Changes of a Newly Established Pleomorphic Malignant Fibrous Histiocytoma Cell Line Am. J. Pathol., August 1, 2004; 165(2): 471 - 480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. Moodley, A. K. Scaffidi, N. L. Misso, C. Keerthisingam, R. J. McAnulty, G. J. Laurent, S. E. Mutsaers, P. J. Thompson, and D. A. Knight Fibroblasts Isolated from Normal Lungs and Those with Idiopathic Pulmonary Fibrosis Differ in Interleukin-6/gp130-Mediated Cell Signaling and Proliferation Am. J. Pathol., July 1, 2003; 163(1): 345 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Krause, N. Scaletta, J.-D. Ji, and L. B. Ivashkiv Rheumatoid Arthritis Synoviocyte Survival Is Dependent on Stat3 J. Immunol., December 1, 2002; 169(11): 6610 - 6616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Deon, S. Ahmed, K. Tai, N. Scaletta, C. Herrero, I.-H. Lee, A. Krause, and L. B. Ivashkiv Cross-Talk Between IL-1 and IL-6 Signaling Pathways in Rheumatoid Arthritis Synovial Fibroblasts J. Immunol., November 1, 2001; 167(9): 5395 - 5403. [Abstract] [Full Text] [PDF]
|
|