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
Autor: | Yunpeng Zhao, Shuai-Shuai Wang, Hua Zhao, Yuanqiang Zhang, Lin Nie, Lei Cheng, Yi Liu, Xiaoqing Wang, Jingkun Li |
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Jazyk: | angličtina |
Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Time Factors medicine.medical_treatment c-Fos p38 Mitogen-Activated Protein Kinases 0302 clinical medicine LBP Phosphorylation Intervertebral Disc Cells Cultured Medicine(all) biology Kinase Interleukin-17 General Medicine Middle Aged musculoskeletal system Cell biology Up-Regulation IL-17 Cytokine 030220 oncology & carcinogenesis Female Interleukin 17 PGE2 medicine.symptom Proto-Oncogene Proteins c-fos COX2 Adult musculoskeletal diseases MAP Kinase Signaling System p38 mitogen-activated protein kinases Inflammation Models Biological General Biochemistry Genetics and Molecular Biology Dinoprostone 03 medical and health sciences Young Adult medicine Humans Protein kinase A business.industry Biochemistry Genetics and Molecular Biology(all) Research JNK Mitogen-Activated Protein Kinases AP-1 MAPK Enzyme Activation Transcription Factor AP-1 030104 developmental biology Cyclooxygenase 2 Immunology biology.protein business |
Zdroj: | Journal of Translational Medicine |
ISSN: | 1479-5876 |
DOI: | 10.1186/s12967-016-0833-9 |
Popis: | 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. Conclusion 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. |
Databáze: | OpenAIRE |
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