Regulation of gingival epithelial cytokine response by bacterial cyclic dinucleotides

Cyclic dinucleotides (cyclic di-guanosine monophosphate (c-di-GMP) and cyclic di-adenosine monophosphate (c-di-AMP)) and lipopolysaccharides (LPS) are pathogen-associated molecular patterns (PAMPs). Individual impacts of PAMPs on immune system have been evaluated, but simultaneous actions of multiple PAMPs have not been studied.

Examination the effects of cyclic dinucleotides and Porphyromonas gingivalis LPS on gingival epithelial cytokine response.

Human gingival keratinocytes (HMK) were incubated with 1, 10, and 100 µM concentrations of c-di-GMP and c-di-AMP, either in the presence or absence of P. gingivalis LPS. Intra- and extracellular levels of interleukin (IL)-1β, IL-8, IL-1Ra, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF), were measured using the Luminex technique.

LPS decreased extracellular IL-8 levels, while the presence of c-di-AMP inhibited this effect. Incubating HMK cells with c-di-AMP (alone or with LPS) elevated the extracellular level of MCP-1. Extracellular VEGF level increased when cells were incubated with LPS and c-di-GMP together, or with c-di-AMP alone. LPS and c-di-AMP suppressed intracellular IL-1β levels. The c-di-AMP elevated intracellular levels of IL-1Ra.

c-di-AMP and, to a lesser extent, c-di-GMP regulate keratinocyte cytokine response, either as an aggregator or as a suppressor of LPS, depending on the cytokine type.