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
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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