Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P05231 (
interleukin-6
)
23,907
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that
interleukin-6
(
IL-6
) alone does not induce osteoclast formation, but soluble
interleukin-6
receptors (sIL-6R) triggered the formation in the presence of
IL-6
in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and
IL-6
in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II,
vacuolar proton-ATPase
and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both
IL-6
and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of
IL-6
and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human
IL-6
and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient
IL-6
and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of
IL-6
and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that
IL-6
in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.
...
PMID:Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. 877 Jul 1
