J Korean Rheum Assoc.  2000 Mar;7(1):43-52.

Activation of Stat Protein in Synovial Cell in Rheumatoid Arthritis

Affiliations
  • 1Department of Internal Medicine, Eulji University, Daejeun, Korea.
  • 2The Hospital for Rheumatic Diseases, Department of Internal Medicine, Hanyang University, Seoul, Korea.
  • 3Department of Pathology, Hanyang University, Seoul, Korea.

Abstract


OBJECTIVE
To characterize Stat activity in synovial tissue in rheumatoid arthritis (RA) in order to see if Stat molecule contributes to the pathogenesis of RA by regulatory expression of genes that play an important role in inflammation and tissue destruction.
METHODS
Synovial tissue were obtained immediately after operative excision. Immuno-histochemistry was done with the antibodies for Stat 3 and Stat 5. Cells were stimulated with interleukin 6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) or steroid using chambered slide. In supershift experiment, cell extracts were incubated with 0.5ng of 32P-labelled double-stranded oligonucleotide probe. Samples were resolved on 4.5% polyacrylamide gels, which was transferred to polyvinylidene fluoride membranes. Anti-phosphotyrosine Stat 3 antibody was used for Western blotting.
RESULTS
Stat 3 was not shown on the synovial tissue section done by immuno-histochemistry. However, activated Stat 3 was expressed on cultured synovial cell stimulated with IL-6 and sIL-6R, and also with IL-6 and dexamethasone using chambered slide. In contrast to Stat 3, activated Stat 5 was expressed on the synovial tissue section, especially around blood vessel.
CONCLUSION
Stat is activated in cultured synovial cells as shown in other immune associated cells, and IL-6 is the strong activator of Stat 3. Further analysis of the regulation of Stats in synovitis and the role of Stats in driving synovial inflammation will yield insight into the pathogenesis of RA and the development of novel therapeutic modality.

Keyword

Rheumatoid arthritis; Signal transduction; Jak-Stat pathway; Interleukin 6; Soluble interleukin 6 receptor

MeSH Terms

Antibodies
Arthritis, Rheumatoid*
Blood Vessels
Blotting, Western
Cell Extracts
Dexamethasone
Fluorides
Gels
Inflammation
Interleukin-6
Membranes
Receptors, Interleukin-6
Signal Transduction
Synovitis
Antibodies
Cell Extracts
Dexamethasone
Fluorides
Gels
Interleukin-6
Receptors, Interleukin-6
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