title: IL-1β/HMGB1 signalling promotes the inflammatory cytokines release via TLR signalling in human intervertebral disc cells.
abstract: Inflammation and cytokines have been recognized to correlate with intervertebral disc (IVD) degeneration (IDD), via mediating the development of clinical signs and symptoms. However, the regulation mechanism remains unclear. We aimed at investigating the regulatory role of interleukin (IL)β and high mobility group box 1 (HMGB1) in the inflammatory response in human IVD cells, and then explored the signalling pathways mediating such regulatory effect. Firstly, the promotion to inflammatory cytokines in IVD cells was examined with ELISA method. And then western blot and real time quantitative PCR were performed to analyse the expression of toll-like receptors (TLRs), receptors for advanced glycation endproducts (RAGE) and NF-κB signalling markers in the IL-1β- or (and) HMGB1-treated IVD cells. Results demonstrated that either IL-1β or HMGB1 promoted the release of the inflammatory cytokines such as prostaglandin E2 (PGE2), TNF-α, IL-6 and IL-8 in human IVD cells. And the expression of matrix metalloproteinases (MMPs) such as MMP-1, -3 and -9 was also additively up-regulated by IL-1β and HMGB1. We also found such additive promotion to the expression of TLR-2, TLR-4 and RAGE, and the NF-κB signalling in intervertebral disc cells. In summary, our study demonstrated that IL-1β and HMGB1 additively promotes the release of inflammatory cytokines and the expression of MMPs in human IVD cells. The TLRs and RAGE and the NF-κB signalling were also additively promoted by IL-1β and HMGB1. Our study implied that the additive promotion by IL-1β and HMGB1 to inflammatory cytokines and MMPs might aggravate the progression of IDD.
authors: Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China.
authors: Fang
authors: F
authors: Fang
authors: Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, 400016, Chongqing, China dianm_jiang@126.com.
authors: Dianming
authors: D
authors: Jiang
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics*; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C000593871:AGER protein, human; D016207:Cytokines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: high mobility group box 1 (HMGB1); interleukin (IL)β; intervertebral disc degeneration (IDD)