title: Enhancement of gingival inflammation induced by synergism of IL-1β and IL-6.
abstract: Internleukin-1 (IL-1) and IL-6 are the most potent proinflammatory cytokines being involved in inflammatory diseases such as periodontitis. The objective of this study was to examine the synergistic effects of IL-1β and IL-6 on gingival inflammation by targeting cultured human gingival fibroblasts (HGFs). HGFs were treated with IL-1β or IL-6/soluble IL-6R (sIL-6R), and total RNA and total cell lysate were collected to examine expression of gp130 known as a signal transducer of IL-6 using qRT-PCR and Western blotting. IL-1β-mediated IL-6 productivity in HGFs was examined using ELISA method. Likewise, after HGFs and THP-1 macrophages were treated with IL-1β, TNF-α and IL-6, sIL-6R productivity was examined. Next, HGFs were treated with IL-6/ sIL-6R after pretreatment of IL-1β, and the intracellular signals were examined using Western blotting. Finally, various mRNA/protein expressions in HGFs treated with IL-6/sIL-6R after pretreatment of IL-1β were examined using qRT-PCR and ELISA method. IL-1β increased significantly both gp130 and IL-6 expression in HGFs. IL-6 increased significantly sIL-6R production in THP-1 macrophages but not HGFs. Co-stimulation with IL-1β and IL-6/sIL-6R induced dramatically the phosphorylation of Stat3, ERK and JNK in HGFs. Interestingly, expression of various inflammation- related molecules such as MMP-1, MCP-1, IL-1ra, bFGF and VEGF were enhanced by co-stimulation with IL-1β and IL-6/sIL-6R in HGFs. Gingival inflammation is regulated by HGFs affected by both IL-1β and IL-6/sIL-6R synergistically through induction of gp130 expression, resulting in progression of periodontitis.
authors: Division of Periodontics, Department of Conservative Dentistry and Oral Rehabilitation, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan.
authors: Shunsuke
authors: S
authors: Sawada
authors: Naoyuki
authors: N
authors: Chosa
authors: Akira
authors: A
authors: Ishisaki
authors: Koji
authors: K
authors: Naruishi
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000235:genetics / Q000378:metabolism; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D010518:Periodontitis / Q000139:chemically induced / Q000473:pathology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D050822:Cytokine Receptor gp130; D048031:JNK Mitogen-Activated Protein Kinases; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1