Differential modulation of human β-defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures

Abstract

Porphyromonas gingivalis lipopolysaccharide (LPS) is a crucial virulence factor strongly involved in the development of chronic periodontitis. It displays a significant amount of lipid A structural heterogeneity, containing both tetra- (LPS1435/1449 ) and penta-acylated (LPS 1690) lipid A structures with opposing effects on E-selectin expression in human endothelial cells. Little is known about how these two isoforms of P. gingivalis LPS could differentially affect host innate immune responses in human gingival epithelia. The present study compares the modulatory effects of P. gingivalis LPS1435/1449 and LPS1690 on the expression of human β-defensins (hBDs) in the reconstituted human gingival epithelium, and examines the involvements of a panel of pattern recognition receptors in the modulatory effects concerned. It is shown that hBD-1, hBD-2 and hBD-3 mRNAs are significantly up-regulated by P. gingivalis LPS1690, but down-regulated by P. gingivalis LPS 1435/1449. Toll-like receptor (TLR) 2 and CD14 mRNAs are also differentially regulated, and the modulation of hBD-2 expression may be through the co-operation of both TLR2 and TLR4. This study suggests that P. gingivalis LPS with different lipid A structures could differentially modulate host innate immune responses in human gingival epithelia, which may be a hitherto undescribed novel pathogenic mechanism of P. gingivalis in periodontal pathogenesis.