Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Targeting Potassium Channels for the Treatment of Rheumatoid Arthritis.

Hu2,  Xueyou, Laragione4,  Teresina, Sun2,  Liang, Koshy2,  Shyny, Jones2,  Karlie R., Horrigan2,  Frank T., Gulko3,  Percio S.

Baylor College of Medicine, Houston, TX
Baylor College of Medicine
Feinstein Institute for Medical Research, Manhasset, NY
Feinstein Institute for Medical Research

Background:

Activated fibroblast-like synoviocytes (FLS) in the rheumatoid arthritis (RA) synovium (RA-FLS) are major players in inflammation, synovium and bone destruction, angiogenesis, and hyperplasia. However, no currently-approved therapies specifically target these cells. Potassium channels regulate cell signaling and thus a large number of functions of non-excitable cells such as fibroblasts, lymphocytes, or astrocytes. We therefore hypothesized that targeting the potassium channels expressed by RA-FLS may represent an attractive target for the treatment of RA.

Methods:

We have used four complementary methods (RT-PCR, western blot, immunocytochemistry, and patch-clamp electrophysiology) to identify the potassium channels expressed by RA-FLS isolated from 5 different patients. We next used selective blockers of KCa1.1 channels (paxilline and iberiotoxin) to probe their roles on RA-FLS proliferation, invasion, and production of cytokines, chemokines, angiogenic factors, and matrix metalloproteinases (MMPs).

Results:

We have identified KCa1.1 channels (BK, Maxi-K, Slo-1) as the major potassium channels expressed by RA-FLS. Blocking KCa1.1 channels inhibited the proliferation of RA-FLS and their ability to produce vascular endothelial growth factor (VEGF), IL-8, and MMP-2 without inducing cytotoxicity or affecting the production of IL-6. In keeping with these data, blocking KCa1.1 channels also inhibited the invasion of RA-FLS in matrigel assays.

Conclusions:

KCa1.1 channels play a major role in the pathogenic functions of RA-FLS. These channels are therefore attractive targets for the treatment of RA.

To cite this abstract, please use the following information:
Hu, Xueyou, Laragione, Teresina, Sun, Liang, Koshy, Shyny, Jones, Karlie R., Horrigan, Frank T., et al; Targeting Potassium Channels for the Treatment of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1128
DOI: 10.1002/art.28895

Abstract Supplement

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