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: Shunsuke Sawada, Naoyuki Chosa, Akira Ishisaki, Koji Naruishi
• Journal: Biomedical research (Tokyo, Japan) (Biomed Res) Vol. 34 Issue 1 Pg. 31-40 (Feb 2013) ISSN: 1880-313X [Electronic] Japan
• PMID: 23428978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1beta
• Interleukin-6
• RNA, Messenger
• STAT3 Transcription Factor
• STAT3 protein, human
• Tumor Necrosis Factor-alpha
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Cytokine Receptor gp130
• JNK Mitogen-Activated Protein Kinases
• MMP1 protein, human
• Matrix Metalloproteinase 1

Topics

• Blotting, Western
• Cell Proliferation (drug effects)
• Cells, Cultured
• Chemokine CCL2 (genetics, metabolism)
• Cytokine Receptor gp130 (genetics, metabolism)
• Drug Synergism
• Fibroblasts (cytology, drug effects, pathology)
• Gene Expression Regulation
• Gingiva (cytology, drug effects, pathology)
• Humans
• Inflammation (pathology)
• Interleukin 1 Receptor Antagonist Protein (genetics, metabolism)
• Interleukin-1beta (pharmacology)
• Interleukin-6 (pharmacology)
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• Matrix Metalloproteinase 1 (genetics, metabolism)
• Periodontitis (chemically induced, pathology)
• Phosphorylation
• RNA, Messenger (genetics, metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction
• Tumor Necrosis Factor-alpha (pharmacology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)