Inhibition of the receptor for advanced glycation inhibits lipopolysaccharide-mediated High mobility group protein B1 and Interleukin-6 synthesis in human gingival fibroblasts through the NF-κB signaling pathway.
AIMS
We investigated the effect of a specific inhibitor of the receptor for advanced glycation (FPS-ZM1) against lipopolysaccharide (LPS)-induced increase in expressions of high mobility group protein B1 (HMGB1) and interleukin-6 (IL-6) in human gingival fibroblasts (HGFs). Furthermore, we explored the potential molecular mechanisms and assessed the involvement of the NF-κB pathway in mediating the changes in the expressions of HMGB1 and IL-6 expression in response to LPS and FPS-ZM1.


METHODS
HGFs were cultured with enzymatic digestion-tissue explants method. The proliferation of LPS-stimulated HGFs pretreated with FPS-ZM1 at 24, 48, and 72 h was determined by cell counting kit 8 assay. The expressions of HMGB1 and IL-6 were measured using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Western blot analysis was used to assess the expressions of receptor for advanced glycation end products (RAGE) and NF-κB.


RESULTS
LPS enhanced the protein expression of RAGE in HGFs. At the same time, LPS stimulated mRNA and protein expressions of HMGB1 and IL-6 in HGFs. However, pretreatment with FPS-ZM1 attenuated these effects. Pretreatment with FPS-ZM1 (250, 500 nM) significantly inhibited the LPS-induced NF-κB activity.


CONCLUSION
FPS-ZM1 down-regulated the LPS-induced HMGB1 and IL-6 expression in HGFs through blocking NF-κB activation. FPS-ZM1 is a promising therapeutic agent for inflammatory diseases caused by oral bacteria.
['Huang|Jialin|J|', 'Xiong|Ting|T|', 'Zhang|Zhenzhen|Z|', 'Tan|Yujie|Y|', 'Guo|Ling|L|']
D001549:Benzamides D005347:Fibroblasts D005881:Gingiva D024243:HMGB1 Protein D006801:Humans D015850:Interleukin-6 D008070:Lipopolysaccharides D016328:NF-kappa B D000067759:Receptor for Advanced Glycation End Products D015398:Signal Transduction
High mobility group protein B1 interleukin-6 Human gingival fibroblasts Lipopolysaccharide NF-κB Pathway Receptor for advanced glycation endproducts