IL37 dampens the IL1β-induced catabolic status of human OA chondrocytes

Abstract

IL37 is induced by IL1β, and IL37 itself reduced IL1β, IL6 and IL8 production, indicating that IL37 is able to induce a counter-regulatory anti-inflammatory feedback loop in chondrocytes. In addition, IL37 dampens catabolic enzyme expression. This supports IL37 as a potential therapeutic target in OA.

IL-37 diminishes proteoglycan loss in human OA cartilage: donor-specific link between IL-37 and MMP-3

“…IL-37 is a suppressor of the innate and adaptive immune system 21e24 . Earlier, we have shown that overexpression of IL-37 in isolated human OA chondrocytes in monolayer decreases not only the expression of pro-inflammatory cytokines but also the expression of cartilage degrading enzymes 25 . These enzymes are known to mediate the degradation of sGAGs in ex vivo cartilage cultures.…”

“…IL-37 protects mice against lung inflammation, arthritis, psoriasis and colitis 21e24 . Previously, we have found that in isolated human OA chondrocytes IL-37 not only reduces IL1b-induced expression of pro-inflammatory cytokines, but also the expression of proteolytic enzymes such as MMP-3, MMP-13 and ADAMTS-5 25 . Therefore, the goal of this study was to investigate if exogenously added recombinant human IL-37 (rhIL-37) protects against sGAG loss in freshly obtained human ex vivo cartilage OA explants and to explore the mechanism behind this protective effect.…”

“…Total RNA was isolated using the RNeasy Fibrous Tissue Mini Kit (Qiagen Inc., Valencia, CA, USA) according to manufacturers protocol. Subsequently, RNA was reverse transcribed with single step RT reaction and quantitative real-time PCR was performed with validated primers, as previously described (Table I) 25 . To calculate the relative gene expression, the reference gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used.…”

The Role of Inflammation in the Pathogenesis of Osteoarthritis

“…IL-37 is a member of the IL-1 family, and it is an antiinflammatory cytokine [53]. Its level has been shown to elevate in osteoarthritis patients [53,54]. IL-37 can reduce the synthesis of proinflammatory cytokines and catabolic enzymes by osteoarthritic chondrocytes and synoviocytes.…”

“…The expression of MMP-13 increased through stimulation by CCL20 [46] and interferon regulatory factor-8 (IRF-8) in chondrocytes derived from patients with osteoarthritis [81]. Conversely, overexpression of IL-37 in chondrocytes decreased the MMP-13 level [53]. Two separate studies by Zhang et al and Wu et al showed that changes in microribonucleic acid (miRNA) expression in osteoarthritis could alter the MMP-13 level [35,51].…”