Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-α-induced genes in bone cells
Open Access
- 10 December 2004
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 77 (3), 388-399
- https://doi.org/10.1189/jlb.0904490
Abstract
The novel cytokine interleukin (IL)-17 has been implicated in many infectious and autoimmune settings, especially rheumatoid arthritis. Consistent with its proinflammatory effects on bone, osteoblast cells are highly responsive to IL-17, particularly in combination with other inflammatory cytokines. To better understand the spectrum of activities controlled by IL-17, we globally profiled genes regulated by IL-17 and tumor necrosis factor α (TNF-α) in the preosteoblast cell line MC3T3-E1. Using Affymetrix microarrays, 80–90 genes were up-regulated, and 19–50 genes were down-regulated with IL-17 and TNF-α as compared with TNF-α alone. These included proinflammatory chemokines and cytokines, inflammatory genes, transcriptional regulators, bone-remodeling genes, signal transducers, cytoskeletal genes, genes involved in apoptosis, and several unknown or unclassified genes. The CXC family chemokines were most dramatically induced by IL-17 and TNF-α, confirming the role of IL-17 as a potent mediator of inflammation and neutrophil recruitment. Several transcription factor-related genes involved in inflammatory gene expression were also enhanced, including molecule possessing ankyrin repeats induced by lipopolysaccharide/inhibitor of κBζ (MAIL/κBζ), CCAAT/enhancer-binding protein δ (C/EBPδ), and C/EBPβ. We also identified the acute-phase gene lipocalin-2 (LCN2/24p3) as a novel IL-17 target, which is regulated synergistically by TNF-α and IL-17 at the level of its promoter. A similar but not identical pattern of genes was induced by IL-17 and TNF-α in ST2 bone marrow stromal cells and murine embryonic fibroblasts. This study provides a profile of genes regulated by IL-17 and TNF-α in osteoblasts and suggests that in bone, the major function of IL-17 is to cooperate and/or synergize with other cytokines to amplify inflammation.Keywords
Funding Information
- National Institutes of Health (AI49329, AI07614)
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