title: Interleukin-17 synergizes with IFNγ or TNFα to promote inflammatory mediator release and intercellular adhesion molecule-1 (ICAM-1) expression in human intervertebral disc cells.
abstract: Interleukin-17 (IL-17) is a cytokine recently shown to be elevated, along with interferon-γ (IFNγ) and tumor necrosis factor (TNFα), in degenerated and herniated intervertebral disc (IVD) tissues, suggesting a role for these cytokines in intervertebral disc disease. The objective of our study was to investigate the involvement of IL-17 and costimulants IFNγ and TNFα in intervertebral disc pathology. Cells were isolated from anulus fibrosus and nucleus pulposus tissues of patients undergoing surgery for intervertebral disc degeneration or scoliosis. The production of inflammatory mediators, nitric oxide (NOx), prostaglandin E2 (PGE2) and interleukin-6 (IL-6), as well as intercellular adhesion molecule (ICAM-1) expression, were quantified for cultured cells following exposure to IL-17, IFNγ, and TNFα. Intervertebral disc cells exposed to IL-17, IFNγ, or TNFα showed a remarkable increase in inflammatory mediator release and ICAM-1 expression (GLM and ANOVA, p < 0.05). Addition of IFNγ or TNFα to IL-17 demonstrated a synergistic increase in inflammatory mediator release, and a marked increase in ICAM-1 expression. These findings suggest that IVD cells not only respond with a catabolic phenotype to IL-17 and costimulants IFNγ and TNFα, but also express surface ligands with consequent potential to recruit additional lymphocytes and immune cells to the IVD microenvironment. IL-17 may be an important regulator of inflammation in the IVD pathologies.
authors.affiliation: Division of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: Gabr
authors.forename: Liufang
authors.initials: L
authors.lastname: Jing
authors.forename: Antonia R
authors.initials: AR
authors.lastname: Helbling
authors.forename: S Michael
authors.initials: SM
authors.lastname: Sinclair
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Allen
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Shamji
authors.forename: William J
authors.initials: WJ
authors.lastname: Richardson
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fitch
authors.forename: Lori A
authors.initials: LA
authors.lastname: Setton
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000276:immunology / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma