Drs Li-Ching Chang and Hsing-Chun Kuo contributed equally to this work.
Regulation of ICAM-1 expression in gingival fibroblasts infected with high-glucose-treated P. gingivalis
Article first published online: 29 APR 2013
© 2013 John Wiley & Sons Ltd
Volume 15, Issue 10, pages 1722–1734, October 2013
How to Cite
Chang, L.-C., Kuo, H.-C., Chang, S.-F., Chen, H. J., Lee, K.-F., Lin, T.-H., Huang, T.-Y., Choe, C.-S., Lin, L.-T. and Chen, C.-N. (2013), Regulation of ICAM-1 expression in gingival fibroblasts infected with high-glucose-treated P. gingivalis. Cellular Microbiology, 15: 1722–1734. doi: 10.1111/cmi.12146
- Issue published online: 15 SEP 2013
- Article first published online: 29 APR 2013
- Accepted manuscript online: 1 APR 2013 02:37AM EST
- Manuscript Accepted: 25 MAR 2013
- Manuscript Revised: 21 MAR 2013
- Manuscript Received: 3 DEC 2012
- Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung Memorial Hospital, and Chang Gung University of Science and Technology, Chia-Yi Campus, Taiwan. Grant Numbers: CLRPG8C0091, CMRPF6A0072, CMRPF6C0031, EZRPF6C0011
- National Science Council, Taiwan. Grant Numbers: NSC101-2622-B-255-001-CC3, NSC 101-2320-B-415-003-MY3
Porphyromonas gingivalis is a major pathogen in the initiation and progression of periodontal disease, which is recognized as a common complication of diabetes. ICAM-1 expression by human gingival fibroblasts (HGFs) is crucial for regulating local inflammatory responses in inflamed periodontal tissues. However, the effect of P. gingivalis in a high-glucose situation in regulating HGF function is not understood. The P. gingivalis strain CCUG25226 was used to study the mechanisms underlying the modulation of HGF ICAM-1 expression by invasion of high-glucose-treated P. gingivalis (HGPg). A high-glucose condition upregulated fimA mRNA expression in P. gingivalis and increased its invasion ability in HGFs. HGF invasion with HGPg induced increases in the expression of ICAM-1. By using specific inhibitors and short hairpin RNA (shRNA), we have demonstrated that the activation of p38 MAPK and Akt pathways is critical for HGPg-induced ICAM-1 expression. Luciferase reporters and chromatin immunoprecipitation assays suggest that HGPg invasion increases NF-κB- and Sp1-DNA-binding activities in HGFs. Inhibition of NF-κB and Sp1 activations blocked the HGPg-induced ICAM-1 promoter activity and expression. The effect of HGPg on HGF signalling and ICAM-1 expression is mediated by CXC chemokine receptor 4 (CXCR4). Our findings identify the molecular pathways underlying HGPg-dependent ICAM-1 expression in HGFs, providing insight into the effect of P. gingivalis invasion in HGFs.