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PMID:17888176

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Citation

Yago, T, Nanke, Y, Kawamoto, M, Furuya, T, Kobashigawa, T, Kamatani, N and Kotake, S (2007) IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats. Arthritis Res. Ther. 9:R96

Abstract

This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.

Links

PubMed PMC2212562 Online version:10.1186/ar2297

Keywords

Animals; Antibodies/administration & dosage; Arthritis, Experimental/metabolism; Arthritis, Experimental/pathology; Arthritis, Experimental/prevention & control; Cells, Cultured; Female; Humans; Interleukin-17/biosynthesis; Interleukin-17/genetics; Interleukin-23/antagonists & inhibitors; Interleukin-23/biosynthesis; Interleukin-23/genetics; Osteoclasts/cytology; Osteoclasts/metabolism; Rats

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IL12B

involved_in

GO:0032740: positive regulation of interleukin-17 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL12B

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL23A

involved_in

GO:0032740: positive regulation of interleukin-17 production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL23A

involved_in

GO:0032729: positive regulation of interferon-gamma production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL23A

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL23R

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000305: curator inference used in manual assertion

GO:0042019

P

Seeded From UniProt

complete

HUMAN:IL23R

involved_in

GO:0032740: positive regulation of interleukin-17 production

ECO:0000305: curator inference used in manual assertion

GO:0042019

P

Seeded From UniProt

complete

HUMAN:TNFA

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL17

involved_in

GO:0045672: positive regulation of osteoclast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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