title: Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment.
abstract: Interleukin (IL)-17 is the founding member of an emerging family of inflammatory cytokines whose functions remain poorly defined. IL-17 has been linked to the pathogenesis of rheumatoid arthritis, and numerous studies implicate this cytokine in inflammation-induced bone loss. It is clear that a major function of IL-17 is to amplify the immune response by triggering production of chemokines, cytokines, and cell-surface markers, ultimately leading to neutrophil chemotaxis and inflammation. As an IL-17 signaling deficiency in mice causes a dramatic reduction in neutrophil chemotaxis and a consequent increased susceptibility to bacterial infection, it is important to define gene targets involved in IL-17-mediated neutrophil trafficking. Here, we demonstrate that IL-17 and tumor necrosis factor alpha (TNF-alpha) cooperatively induce the lipopolysaccharide-inducible CXC chemokine (LIX; a.k.a., CXC chemokine ligand 5, Scya5, or murine granulocyte chemotactic protein-2) in the preosteoblast cell line MC3T3. LIX is induced rapidly at the mRNA and protein levels, likely through the activation of new gene transcription. Conditioned media from MC3T3 cells treated with IL-17 and/or TNF-alpha stimulates neutrophil mobility potently, and LIX is a significant contributing factor to this process. In addition, IL-17 cooperates with bacterial components involved in periodontal disease to up-regulate LIX expression. This study is the first demonstration of LIX expression in bone cells and has implications for inflammatory bone diseases such as arthritis and periodontal disease.
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo, SUNY, 36 Foster Hall, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ruddy
authors.forename: Fang
authors.initials: F
authors.lastname: Shen
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Smith
authors.forename: Ashu
authors.initials: A
authors.lastname: Sharma
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Gaffen
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology; D015152:Blotting, Northern; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000096:biosynthesis*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology*; D010510:Periodontal Diseases / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; C094739:Cxcl5 protein, mouse; D020381:Interleukin-17; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha