Differential induction of IL‐1β and IL‐6 production by the nontoxic lipid A from Porphyromonas gingivalis in comparison with synthetic Escherichia coli lipid A in human peripheral blood mononuclear cells

Porphyromonas gingivalis 381 lipid A possesses 1‐phospho β(1–6)‐linked glucosamine disaccharide with 3‐hydroxy‐15‐methylhexadecanoyl and 3‐hexadecanoyloxy‐15‐methylhexadecanoyl groups at the 2‐ and 2′‐positions, respectively. P. gingivalis lipid A indicated lower activities in inducing interleukin‐1β (IL‐1β) mRNA expression, pro‐IL‐1β protein synthesis and IL‐1β production than those of synthetic Escherichia coli lipid A (compound 506) in human peripheral blood mononuclear cells (PBMC). The induction of IL‐6 mRNA and IL‐6 synthesis by P. gingivalis lipid A were comparable to those of compound 506. Herbimycin A, H‐7 and H‐8, inhibitors of tyrosine kinase, protein kinase C and cyclic nucleotide‐dependent protein kinase, inhibited P. gingivalis lipid A‐ and compound 506‐induced IL‐1β and IL‐6 synthesis. W‐7, an inhibitor of calmodulin (CaM) kinase, inhibited only P. gingivalis lipid A‐induced IL‐1β production. The result suggests that the CaM kinase‐dependent cascade is involved in the down‐regulation of IL‐1β production by P. gingivalis lipid A. P. gingivalis lipid A and compound 506 also functioned in the induction of tyrosine and serine/threonine phosphorylation of several proteins in PBMC. P. gingivalis lipid A inhibited specific binding of fluorescein‐labelled E. coli LPS to the PBMC. The nontoxic lipid A of P. gingivalis , having a chemical structure different from toxic compound 506, appears to induce the up‐ and down‐regulation of the differential cytokine‐producing activities following the activation of various intracellular enzymes including the CaM kinase through the common receptor sites of LPS.