2024 Volume 22 Issue 4 Pages 165-177
Hyperglycemia is a major factor of diabetes. Respiratory symptoms are frequently observed in people with diabetes. It is well known that periodontitis is associated with developmental of diabetes. Fusobacterium nucleatum（F. nucleatum）is one of major pathogen of periodontitis. Isolation frequency of F. nucleatum in gingival crevicular fluid of diabetes patients is greater than those in non-diabetes control and, furthermore, also positively correlated with fasting blood glucose and glycated hemoglobin levels. In addition, F. nucleatum exacerbates chronic obstructive pulmonary disease. Therefore, we examined the effect of F. nucleatum on human bronchial fibroblasts（HBFs）cultured in normal glucose（NG）, high glucose（HG）and NG with mannitol as osmotic control （MG）.
We performed invasion assay for F. nucleatum into HBFs and examined the protein and mRNA expressions of intercellular adhesion molecule-1（ICAM-1）. We next examined the protein expressions of toll-like receptor（TLR）2, TLR4 and the receptors for advanced glycation end products（RAGE）in HBFs inoculated with F. nucleatum. We analyzed mRNA expression of interleukin-6（IL-6）triggered by TLR2, TLR4 and RAGE. In addition, we confirmed IL-6 production in HBFs pre-treated with inhibitors of nuclear factor-kappa B（NF-κB）and extracellular signal-regulated kinase 1/2（ERK1/2）before inoculation with F. nucleatum.
The numbers of intracellular F. nucleatum were significantly higher in HG group than in NG group. The protein and mRNA expressions of ICMA-1 were increased in HG group inoculated with F. nucleatum. The protein expressions of TLR2, TLR4 and RAGE and mRNA expression of IL-6 were enhanced in HG group inoculated with F. nucleatum. In addition, IL-6 production was reduced by inhibitors of NF-κB and ERK1/2.
Our results indicated that HG promoted the invasion of F. nucleatum through ICAM-1 expression in HBFs. We propose that HG-induced over expression of TLR2, TLR4 and RAGE leads to mRNA expression of IL-6 through NF-κB and ERK1/2.
