Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 14, Pages -Publisher
MDPI
DOI: 10.3390/ijms22147633
Keywords
neutrophil extracellular traps; interleukin-6; citrullinated proteins; rheumatoid arthritis
Funding
- Japan Society for the Promotion of Science [21H02959, 18K08403]
- Grants-in-Aid for Scientific Research [21H02959, 18K08403] Funding Source: KAKEN
Ask authors/readers for more resources
Neutrophils and their extracellular traps are important in the pathogenesis of rheumatoid arthritis, with IL-6 enhancing neutrophil chemotaxis and NETosis in inflammatory joints, possibly being the source of citrullinated proteins.
Neutrophils and their extracellular traps have been shown to play an important role in the pathogenesis of rheumatoid arthritis (RA), but the detailed mechanisms in joints are still unclear, and their regulation remains to be solved. Here, we explored neutrophil extracellular trap (NET)osis in experimental models of arthritis and further investigated the effects of interleukin-6 (IL-6) inhibition in neutrophils and NETosis. In skins of peptide GPI-induced arthritis (pGIA), citrullinated protein was detected as well as citrullinated histone expression in immunized skin but this was not specific to pGIA. Citrullinated histone expression in pGIA joints was specific to pGIA and was merged with neutrophil elastase, suggesting NETosis. Neutrophils in joints tend to upregulate IL-6 receptors when compared with bone marrow neutrophils. Administration of mouse anti-IL-6 receptor antibodies in pGIA suppressed arthritis in association with a decrease in neutrophil infiltration and NETosis in joints. In the plasma of RA patients, citrullinated protein was significantly reduced after tocilizumab treatment. Our results suggest that IL-6 enhances neutrophil chemotaxis and NETosis in inflammatory joints and could be the source of citrullinated proteins.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available