High Molecular Weight Hyaluronic Acid Regulates P. Gingivalis-induced Inflammation and Migration in Human Gingival Fibroblasts Via MAPK and NF-κB Signaling Pathway

Chronic periodontitis is associated with Porphyromonas gingivalis (P. gingivalis) infection. Hyaluronic Acid (HA), a critical component of the extracellular matrix, exhibits anti-inflammatory and wound-healing properties. This study aimed to investigate the effect of various molecular weights of HA (30, 300 and 1300 kDa) on P. gingivalis-induced inflammatory and wound-healing responses in human gingival fibroblasts (HGFs). Cell cytotoxicity and proliferation were assessed by Lactate dehydrogenase and MTT assays, respectively. An enzyme linked immunosorbent assay was used to detect the levels of interleukin (IL) -1β, IL-6, IL-8, IL-4 and IL-10. Cell migration was evaluated with a scratch wound healing assay. The expression of nuclear factor kappa B (NF-кB), IкBα, p38 and extracellular signal-regulated kinase (ERK) were analyzed with Western blotting. The results showed that P. gingivalis (1.6 × 10 CFU/mL) and HA (1, 2, 5 and 10 mg/mL) exhibited no toxicity to the HGFs. The 1300 kDa HA inhibited P. gingivalis-induced IL-1β, IL-6, IL-8, IL-4 and IL-10 production in a dose-dependent manner, while the 30 and 300 kDa HA did not have an effect. Meanwhile, cell migration was significantly promoted by the 30 and 1300 kDa HA. Furthermore, the 1300 kDa HA inhibited NF-κB expression, IκBα degradation and P. gingivalis-induced ERK and P38 activation. Therefore, our study suggests that high molecular weight HA may have beneficial effects on periodontal inflammation and oral wounds.