Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity differentially modulates the expression of IL-6 and IL-8 in human gingival fibroblasts

Herath TDK, Wang Y, Seneviratne CJ, Lu Q, Darveau RP, Wang CY, Jin L. Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity differentially modulates the expression of IL-6 and IL-8 in human gingival fibroblasts. J Clin Periodontol 2011; 38: 694–701. doi: 10.1111/j.1600-051X.2011.01741.x. Aim: Porphyromonas gingivalis lipopolysaccharide (LPS) displays a significant amount of structural heterogeneity, containing both tetra- (LPS1435/1449) and penta-acylated (LPS1690) lipid A structures. This study investigated the effects of the two isoforms of P. gingivalis LPS on the expression of IL-6, IL-8 and TNF-α in human gingival fibroblasts (HGFs). Materials and methods: HGFs were stimulated with P. gingivalis LPS1435/1449 and LPS1690 in both dose- (1 ng–10 μg/ml) and time-dependent (2–48 h) experiments. Total RNA and protein were extracted and used for analysis of the IL-6, IL-8 and TNF-α transcripts as well as IL-6 and IL-8 proteins, by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: P. gingivalis LPS1690 significantly up-regulated the mRNA and protein expression of IL-6 and IL-8, whereas P. gingivalis LPS1435/1449 did not induce significant host response. The expression levels of IL-6 and IL-8 up-regulated by P. gingivalis LPS1690 continuously increased with time course. In contrast, TNF-α transcript expression was up-regulated promptly by P. gingivalis LPS1690 after 2 h of stimulation and gradually declined afterwards. Conclusions: This study suggests that P. gingivalis LPS heterogeneity may differentially modulate the pro-inflammatory cytokine expression in HGFs, which may contribute to periodontal pathogenesis.