title: The chemokine, CXCL16, and its receptor, CXCR6, are constitutively expressed in human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL-1ß in vitro.
abstract: Chemokines are an important group of soluble molecules with specialized functions in inflammation. The roles of many specialized chemokines and their receptors remain poorly understood in the human intervertebral disc. We investigated CXCL16 and its receptor, CXCR6, to determine their immunolocalization in disc tissue and their presence following exposure of cultured human annulus fibrosus cells to proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can induce hypoxia-inducible factor 1α (HIF-1α), which is a phenotypic marker of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in many cells of the annulus portion of the disc. Molecular studies showed that annulus fibrosus cells exposed to IL-1ß, but not TNF-α, exhibited significant up-regulation of CXCL16 expression vs. control cells. There was no significant difference in the percentage of annulus cells that exhibited immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens. The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests the need for future research concerning the role of this chemokine in proinflammatory functions, HIF-1α expression and disc vascularization.
authors.affiliation: a Department of Orthopaedic Surgery , Carolinas Medical Center , Charlotte , North Carolina.
authors.forename: H E
authors.initials: HE
authors.lastname: Gruber
authors.affiliation: a Department of Orthopaedic Surgery , Carolinas Medical Center , Charlotte , North Carolina.
authors.forename: E
authors.initials: E
authors.lastname: Marrero
authors.affiliation: a Department of Orthopaedic Surgery , Carolinas Medical Center , Charlotte , North Carolina.
authors.forename: J A
authors.initials: JA
authors.lastname: Ingram
authors.affiliation: a Department of Orthopaedic Surgery , Carolinas Medical Center , Charlotte , North Carolina.
authors.forename: G L
authors.initials: GL
authors.lastname: Hoelscher
authors.affiliation: a Department of Orthopaedic Surgery , Carolinas Medical Center , Charlotte , North Carolina.
authors.forename: E N
authors.initials: EN
authors.lastname: Hanley
mesh_terms: D000070616:Annulus Fibrosus / Q000166:cytology / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D021381:Protein Transport; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D053583:Interleukin-1beta; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha
keywords: CXCL16; CXCR6; IL-1α; TNF-ß; annulus fibrosus; cell culture; intervertebral disc; nucleus pulposus