Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130

Nowell, Mari Ann, Richards, Peter James, Horiuchi, Sankichi, Yamamoto, Naoki, Rose-John, Stefan, Topley, Nicholas, Williams, Anwen Sian ORCID: https://orcid.org/0000-0001-6118-020X and Jones, Simon Arnett ORCID: https://orcid.org/0000-0001-7297-9711 2003. Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. The Journal of Immunology 171 (6) , pp. 3202-3209.

Full text not available from this repository.

Abstract

Studies in IL-6-deficient (IL-6-/-) mice highlight that IL-6 contributes to arthritis progression. However, the molecular mechanism controlling its activity in vivo remains unclear. Using an experimental arthritis model in IL-6-/- mice, we have established a critical role for the soluble IL-6R in joint inflammation. Although intra-articular administration of IL-6 itself was insufficient to reconstitute arthritis within these mice, a soluble IL-6R-IL-6 fusion protein (HYPER-IL-6) restored disease activity. Histopathological assessment of joint sections demonstrated that HYPER-IL-6 increased arthritis severity and controlled intrasynovial mononuclear leukocyte recruitment through the CC-chemokine CCL2. Activation of synovial fibroblasts by soluble IL-6R and IL-6 emphasized that these cells may represent the source of CCL2 in vivo. Specific blockade of soluble IL-6R signaling in wild-type mice using soluble gp130 ameliorated disease. Consequently, soluble IL-6R-mediated signaling represents a promising therapeutic target for the treatment of rheumatoid arthritis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
Systems Immunity Research Institute (SIURI)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 17 Oct 2022 08:29
URI: https://orca.cardiff.ac.uk/id/eprint/286

Citation Data

Cited 212 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item