title: Interleukin-17 upregulates vascular endothelial growth factor by activating the JAK/STAT pathway in nucleus pulposus cells.
abstract: OBJECTIVE
  Intervertebral disc (IVD) related diseases and age-related IVD degeneration are responsible for significant morbidity. Inflammatory mediators and pro-inflammatory cytokines, including interleukin (IL)-17, show elevated expression in degenerated disc tissue. IL-17 is reported to transduce signals across the cell membrane predominantly via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signal transduction pathway, leading to transcriptional activation of target genes.
  
  
  METHODS
  In this study, we investigated whether the JAK/STAT pathway plays a role in IL-17-mediated signaling in the nucleus pulposus (NP) cells of IVDs. Vascular endothelial growth factor (VEGF) and IL-17 were found to be highly expressed in human degenerated NP tissue. In isolated rat NP cells, IL-17-induced VEGF expression in a time- and dose-dependent manner. Rat NP cells were co-transfected with VEGF promoter plasmid along with constitutively active STAT1, STAT3 or JAK2 plasmid. VEGF promoter activity was found to be increased by STAT1, STAT3 and JAK2 in IL-17-treated cells. Transfection of cultured rat NP cells with STAT1 or STAT3 lentiviral short hairpin RNAs or treatment with the JAK2 inhibitor AG490 significantly reduced IL-17-stimulated VEGF expression.
  
  
  CONCLUSIONS
  IL-17 upregulated VEGF expression in rat NP cells mediated by the JAK/STAT pathway, and elevated levels of IL-17 and VEGF are present in human degenerated NP tissue. These findings provide new insight into the pathology of IVD degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Jianxi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. Electronic address: doctorchj@126.com.
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000096:biosynthesis*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism* / Q000473:pathology; D053612:Janus Kinases / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D000070614:Nucleus Pulposus / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D050791:STAT Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D020381:Interleukin-17; D050791:STAT Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D053612:Janus Kinases
keywords: Interlekin-17; Intervertebral disc; JAK/STAT pathway; Nucleus pulposus; VEGF