IL‐37b alleviates inflammation in the temporomandibular joint cartilage via IL‐1R8 pathway

Abstract

Objectives Interleukin (IL)‐37 is a natural suppressor of innate inflammation. This study was conducted to explore the anti‐inflammatory effects of IL‐37 in temporomandibular joint (TMJ) inflammation. Materials and Methods The expression of IL‐37 in the TMJ was measured using ELISA and IHC. Human TMJ chondrocytes were treated with IL‐37b and IL‐1β, and inflammation‐related factors were detected. siRNA‐IL‐1R8 was transfected into chondrocytes, and the affected pathways were detected. IL‐37b was used in disc‐perforation‐induced TMJ inflammation in SD rats. Micro‐CT, IHC, real‐time PCR and histological staining were used to quantify the therapeutic effect of IL‐37b. Results IL‐37 was expressed in the synovium and the disc of patients with osteoarthritis (OA) and in the articular cartilage of condylar fracture patients. IL‐37 was highly expressed in synovial fluid of patients with synovitis than in those with OA and disc displacement and was closely related to visual analogue scale (VAS) score. In vitro, IL‐37b suppressed the expression of pro‐inflammatory factors. In addition, IL‐37b exerted anti‐inflammatory effects via IL‐1R8 by inhibiting the p38, ERK, JNK and NF‐κB activation, while silencing IL‐1R8 led to inflammation and upregulation of these signals. In disc‐perforation‐induced TMJ inflammation in SD rats, IL‐37b suppressed inflammation and inhibited osteoclast formation to protect against TMJ. Conclusions IL‐37b may be a novel therapeutic agent for TMJ inflammation.

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

“…However, as described above, IL-37 plays an important anti-inflammatory and immunomodulatory capacity in a variety of inflammatory and autoimmune diseases. In addition, IL-37 in vivo could inhibit NLRP3 activation also be mentioned in colitis and LPS-induced disease [19,22,[35][36][37]. In recent study, Rudloff et al reported that IL-37 significantly suppress inflammasome activity in vivo to ameliorate inflammasome-driven diseases, which could corroborate our study results to some extent [38].…”

IL-37 Gene Modification Enhances the Protective Effects of Mesenchymal Stromal Cells on Intestinal Ischemia Reperfusion Injury

“…However, as described above, IL-37 plays an important anti-inflammatory and immunomodulatory capacity in a variety of inflammatory and autoimmune diseases. In addition, IL-37 in vivo could Stem Cells International inhibit NLRP3 activation also in colitis-and LPS-induced disease [19,22,[35][36][37]. In a recent study, Rudloff et al reported that IL-37 significantly suppresses inflammasome activity in vivo to ameliorate inflammasome-driven diseases, which could corroborate our study results to some extent [38].…”

TLR4 contributes to the damage of cartilage and subchondral bone in discectomy‐induced TMJOA mice

“…15,45 Additionally, various joint-derived cell studies, such as synovial fibroblasts, chondrocytes and osteoblasts studies as well, used IL-1β as one of TMJOA stimulators. [46][47][48][49] Thus, we uti- In the present study, the elevation of TLR4 was accompanied by the augmentation of MyD88, NFκB p65 as well as pro-inflammatory and catabolic mediators both in discectomy-induced TMJOA mice and in IL-1β-induced chondrocytes, and vice versa. Although these findings cannot illustrate the explicit mechanism that how TLR4 manipulates TMJOA progression, it is strongly indicated that TLR4 contributes to the damage of cartilage and subchondral bone during TMJOA progression through activation of MyD88/NFκB to release the pro-inflammatory and catabolic mediators, as the role of TLR4/ MyD88/NFκB signal pathway in regulating inflammatory mediators has been specified in varied diseases.…”

“…The abundance of IL‐1β in joint is a striking feature of TMJOA development 15,45 . Additionally, various joint‐derived cell studies, such as synovial fibroblasts, chondrocytes and osteoblasts studies as well, used IL‐1β as one of TMJOA stimulators 46‐49 . Thus, we utilized IL‐1β stimulating chondrocytes to mimic TMJOA condition in vitro.…”