Transforming growth factor beta induces interleukin-11 expression in osteoarthritis

Abstract

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and possesses both pro- and anti-inflammatory properties. IL-11 activates its target cells via binding to a membrane-bound IL-11R and subsequent formation of a homodimer of the signal-transducing receptor gp130. Thus, the expression pattern of the IL-11R determines which cells can be activated by IL-11. However, knowledge about IL-11 target cells and cells that secrete IL-11 are sparse, and the overall roles of IL-11 in inflammatory diseases are largely unexplored. In this study, we show that high amounts of IL-11 can be detected via ELISA in the synovial fluid of osteoarthritis (OA) patients in comparison to rheumatoid arthritis (RA) patients. Using primary cells and tissue of OA patients, we show that IL-11 is expressed by chondrocytes in cartilage, but not in the synovium. We further identify the cytokine transforming growth factor β 1(TGF-β1) as a potent inducer of IL-11 secretion in both primary chondrocytes and fibroblasts, and TGF-β1 and IL-11 levels correlate significantly in the synovial fluid of OA patients. Using immunohistochemistry, we show that both cartilage and synovium express IL-11R, and the amount of IL-11R is independent of the disease severity. Primary chondrocytes and fibroblasts from OA patients respond to IL-11 stimulation with potent activation of the Jak/STAT3 signaling cascade, suggesting that these cell types are not only the source, but also the targets of IL-11 in OA patients. Our results uncover IL-11 as a potential new target for therapy in OA.