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- Title
Expression Profile of Human Gingival Fibroblasts Induced by Interleukin-1β Reveals Central Role of Nuclear Factor-Kappa B in Stabilizing Human Gingival Fibroblasts During Inflammation.
- Authors
Vardar-Sengul, Saynur; Arora, Shilpi; Baylas, Haluk; Mercola, Dan
- Abstract
Background: Interleukin (IL)-1β is a key cytokine in the pathogenesis of periodontitis, and it induces inflammatory mediators in periodontal diseases. We developed immortalized human gingival fibroblasts (HGFs), investigated the effects of IL-1β on the gene expression using expression arrays containing ~40,000 genes, and tested the role of nuclear factor-kappa B (NF-κB) in maintaining an activated HGF population. Methods: Total RNA was isolated from IL-1β-induced and mock-induced control cells. Gene expression analyses were performed using expression arrays and confirmed by quantitative real-time polymerase chain reaction. Western blot analysis to show inhibitor of kappa B-alpha (IκBα phosphorylation and immunostaining of cells for NF-κB nuclear translocation were performed. Apoptosis was confirmed by assay of poly ADP-ribose polymerase (PARP) cleavage. Results: A total of 382 probe sets corresponding to 254 genes were differentially expressed in IL-1β-induced cells (P <0.001 ). A total of 215 genes were upregulated, and 39 genes were downregulated. Most notable NF-κB pathway members (NFκB1, NFκB2, IκBα, IκB∈, IκBζ, REL, RELB, and TA-NFKBH) were upregulated. IκBα was phosphorylated, and NF-κB accumulated in the nucleus. An IL-1β-induced set of 27 genes was downregulated by an NF-κB inhibitor, leading to a decreased number of viable cells and suggesting an antiapoptotic role for NF-κB. Conclusions: IL-1β leads to a large number of significant expression changes consistent with a pathologic role in periodontitis, including enhancement of inflammatory cytokines, chemokines, transcription factors, matrix metalloproteinases, adhesion molecules, and especially NF-κB-dependent antiapoptotic genes. NF-κB activation blocks apoptosis, thereby stabilizing the HGF population in inflammation.
- Subjects
FIBROBLASTS; INTERLEUKIN-1; NF-kappa B; CYTOKINES; PERIODONTITIS; INFLAMMATORY mediators; PERIODONTAL disease; GENE expression
- Publication
Journal of Periodontology, 2009, Vol 80, Issue 5, p833
- ISSN
0022-3492
- Publication type
Article
- DOI
10.1902/jop.2009.080483