title: 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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Jing-kun
authors.initials: JK
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Nie
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Yun-peng
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Yuan-qiang
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai, 200011, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Shuai-shuai
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, People's Republic of China. chengleiyx@126.com.|Qilu Hospital Shandong University, No.107, Wen Hua Xi Road, Jinan, 250012, Shandong, People's Republic of China. chengleiyx@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D020381:Interleukin-17 / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020381:Interleukin-17; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: AP-1; COX2; IL-17; LBP; MAPK; PGE2