IL-17 mediates inflammatory reactions via p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cells

• Published in: Journal of translational medicine 2016-03, Vol.14 (77), p.77, Article 77
• Main Authors: Li, Jing-kun, Nie, Lin, Zhao, Yun-peng, Zhang, Yuan-qiang, Wang, Xiaoqing, Wang, Shuai-shuai, Liu, Yi, Zhao, Hua, Cheng, Lei
• Format: Article
• Language: English
• Subjects: Adult; Care and treatment; Cells, Cultured; COX-2 inhibitors; Cyclooxygenase 2 - metabolism; Dinoprostone - biosynthesis; Dosage and administration; Enzyme Activation - drug effects; Female; Health aspects; Humans; Inflammation; Inflammation - metabolism; Inflammation - pathology; Interleukin-17 - pharmacology; Interleukins; Intervertebral Disc - pathology; JNK Mitogen-Activated Protein Kinases - metabolism; Low back pain; Male; MAP Kinase Signaling System - drug effects; Middle Aged; Models, Biological; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Protein kinases; Proto-Oncogene Proteins c-fos - metabolism; Risk factors; Time Factors; Transcription Factor AP-1 - metabolism; Up-Regulation - drug effects; Young Adult
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-016-0833-9

Low back pain and sciatica caused by intervertebral disc (IVD) disease are associated with inflammatory responses. The cytokine interleukin 17 (IL-17) is elevated in herniated and degenerated IVD tissues and acts as a regulator of disc inflammation. The objective of this study was to investigate the involvement of IL-17A in IVD inflammatory response and to explore the mechanisms underlying this response. Cells were isolated from nucleus pulposus (NP) tissues collected from patients undergoing surgeries for IVD degeneration. The concentrations of COX2 and PGE2, as well as of select proteins involved in the mitogen-activated protein kinase (MAPK)/activating protein-1 (AP-1) pathway, were quantified in NP cells after exposure to IL-17 with or without pretreatment with MAPK or AP-1 inhibitors. Our results showed that IL-17A increased COX2 expression and PGE2 production via the activation of MAPKs, including p38 kinase and Jun N-terminal kinase (JNK). Moreover, IL-17A-induced COX2 and PGE2 production was shown to rely on p38/c-Fos and JNK/c-Jun activation in an AP-1-dependent manner. In summary, our results indicate that IL-17A enhances COX2 expression and PGE2 production via the p38/c-Fos and JNK/c-Jun signalling pathways in NP cells to mediate IVD inflammation.