Importance of NF-{kappa}B in rheumatoid synovial tissues: in situ NF-{kappa}B expression and in vitro study using cultured synovial cells

doi:10.1136/ard.60.7.678

Annals of the Rheumatic Diseases 2001;60:678-684; doi:10.1136/ard.60.7.678

Ann Rheum Dis 2001;60:678-684 ( July )

Extended report

Importance of NF- $kappa$ B in rheumatoid synovial tissues: in situ NF- $kappa$ B expression and in vitro study using cultured synovial cells S Yamasaki^a, A Kawakami^a, T Nakashima^b, H Nakamura^a, M Kamachi^a, S Honda^a, Y Hirai^a, A Hida^a, H Ida^a, K Migita^a, Y Kawabe^a, T Koji^c, I Furuichi^d, T Aoyagi^d, K Eguchi^a

^a The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan, ^b Department of Hospital Pharmacy, Nagasaki University School of Medicine, ^c Department of Histology and Cell Biology, Nagasaki University School of Medicine, ^d Department of Orthopaedics, National Ureshino Hospital, Saga, Japan

Correspondence to: Professor K Eguchi, The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan eguchi{at}net.nagazaki-u.ac.jp

Accepted for publication 15 November 2000

OBJECTIVES $---$ To examine whether inhibition of NF- $kappa$ B induces apoptosis of human synovial cells stimulated by tumour necrosis factor $alpha$ (TNF $alpha$ ),interleukin 1 $beta$ (IL1 $beta$ ), and anti-Fas monoclonal antibody(mAb).
METHODS $---$ The expression of proliferating cell nuclear antigen (PCNA), NF- $kappa$ B, and the presence of apoptotic synovial cells were determinedin synovial tissues. Apoptosis of cultured synovial cells wasinduced by inhibition of NF- $kappa$ B nuclear translocation by Z-Leu-Leu-Leu-aldehyde(LLL-CHO). The activation of caspase-3 and expression of XIAPand cIAP2 in synovial cells in LLL-CHO induced apoptosis was alsoexamined.
RESULTS $---$ Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cellswere also detected in the RA synovial tissues. Nuclear NF- $kappa$ B wasexpressed in RA synovial cells. Electrophoretic mobility shiftassay showed that treatment of cells with TNF $alpha$ or IL1 $beta$ significantlystimulated nuclear NF- $kappa$ B activity. A small number of apoptoticsynovial cells expressing intracellular active caspase-3 werefound after treatment of cells with LLL-CHO. Although treatmentof RA synovial cells with TNF $alpha$ or IL1 $beta$ alone did not induce apoptosis,apoptosis induced by LLL-CHO and caspase-3 activation were clearlyenhanced in TNF $alpha$ or IL1 $beta$ stimulated synovial cells compared withunstimulated synovial cells. Furthermore, induction of apoptosisof synovial cells with caspase-3 activation by anti-Fas mAb wasclearly increased by LLL-CHO. The expression of cIAP2 and XIAPin synovial cells may not directly influence the sensitivity ofsynovial cells to apoptosis induced by LLL-CHO.
CONCLUSION $---$ The results suggest that NF- $kappa$ B inhibition may be a potentially important therapeutic approach for RA by correcting the imbalancebetween apoptosis and proliferation of synovial cells in RA synovialtissue.

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Technorati What's this?

This article has been cited by other articles:

Simmonds, R. E., Foxwell, B. M. (2008). Signalling, inflammation and arthritis: NF-{kappa}B and its relevance to arthritis and inflammation. Rheumatology (Oxford) 47: 584-590 [Abstract] [Full Text]
Yamaza, T., Masuda, K.F., Atsuta, I., Nishijima, K., Kido, M.A., Tanaka, T. (2004). Oxidative Stress-induced DNA Damage in the Synovial Cells of the Temporomandibular Joint in the Rat. JDR 83: 619-624 [Abstract] [Full Text]
Ishikawa, H, Nakao, K, Matsumoto, K, Nishimura, D, Ichikawa, T, Hamasaki, K, Eguchi, K (2004). Bone marrow engraftment in a rodent model of chemical carcinogenesis but no role in the histogenesis of hepatocellular carcinoma. Gut 53: 884-889 [Abstract] [Full Text]
Kawakami, A, Urayama, S, Yamasaki, S, Hida, A, Miyashita, T, Kamachi, M, Nakashima, K, Tanaka, F, Ida, H, Kawabe, Y, Aoyagi, T, Furuichi, I, Migita, K, Origuchi, T, Eguchi, K (2004). Anti-apoptogenic function of TGF{beta}1 for human synovial cells: TGF{beta}1 protects cultured synovial cells from mitochondrial perturbation induced by several apoptogenic stimuli. Ann Rheum Dis 63: 95-97 [Abstract] [Full Text]
Seemayer, C. A., Kuchen, S., Kuenzler, P., Rihoskova, V., Rethage, J., Aicher, W. K., Michel, B. A., Gay, R. E., Kyburz, D., Neidhart, M., Gay, S. (2003). Cartilage Destruction Mediated by Synovial Fibroblasts Does Not Depend on Proliferation in Rheumatoid Arthritis. Am. J. Pathol. 162: 1549-1557 [Abstract] [Full Text]
Yamaza, T., Masuda, K.F., Tsukiyama, Y., Nishijima, K., Murakami, R., Kido, M.A., Koyano, K., Tanaka, T. (2003). NF-{kappa}B Activation and iNOS Expression in the Synovial Membrane of Rat Temporomandibular Joints after Induced Synovitis. JDR 82: 183-188 [Abstract] [Full Text]
Sonis, S. T. (2002). THE BIOLOGIC ROLE FOR NUCLEAR FACTOR-KAPPAB IN DISEASE AND ITS POTENTIAL INVOLVEMENT IN MUCOSAL INJURY ASSOCIATED WITH ANTI-NEOPLASTIC THERAPY. CROBM 13: 380-389 [Abstract] [Full Text]

Services

Citing Articles

Google Scholar

PubMed

Topic Collections

Bookmark with

What's this?

Register for free content

The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.