Interleukin-17 regulates expression of the CXC chemokine LIX/CXCL5 in osteoblasts: implications for inflammation and neutrophil recruitment

Journal of Leukocyte Biology

Jeffrey B. Smith¹  Sarah L. Gaffen²  Matthew J. Ruddy³  Fang Shen⁴  Ashu Sharma⁴ 

[1] Division of Neonatology of the Department of Pediatrics, David Geffen School of Medicine and Mattel Children’s Hospital at UCLA, University of California, Los Angeles Division of Neonatology of the Department of Pediatrics, David Geffen School of Medicine and Mattel Children’s Hospital at UCLA, University of California, Los Angeles Division of Neonatology of the Department of Pediatrics, David Geffen School of Medicine and Mattel Children’s Hospital at UCLA, University of California, Los Angeles;Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and;Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and Departments of Microbiology and Immunology, School of Medicine and Biomedical Sciences, and;Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and Oral Biology, School of Dental Medicine, University at Buffalo, SUNY, New York; and

关键词: TNF-α;    cytokine;    synergy;    bone cells;    GCP-2;   

DOI  :  10.1189/jlb.0204065

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 α (TNF-α) 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-α 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.

【 授权许可】

Unknown