GABA_B Receptors as Modulating Target for Inflammatory Responses of the Periodontal Ligament

PDL cells express GABA_B1 and GABA_B2 receptors, which are regulated by inflammation and thus might be implicated in periodontal immunology. It was the aim of this study to elucidate the functional role of GABA_B receptors in immunomodulation regarding activation of proregenerative versus proinflammatory mechanisms. Human PDL cells were exposed to GABA and/or GABA_B receptor antagonist CGP-52432 alone or in combination with IL-1β to mimic inflammation. The influence on marker expression for inflammatory tissue destruction was determined via qRT-PCR and Luminex assays. Proliferation and biomineralization were assessed by MTS assay and von Kossa staining. Statistical significance was set at p < 0.05. GABA_B receptor blockade inhibited expression of IL-6, TNFα, MMP-3, and MMP-8 in an inflammatory milieu on transcriptional and on protein level, mediated by NF-κB. Besides, receptor blockade enhanced proliferation, especially under inflammatory conditions, and reduced mineralization in a non-inflammatory milieu. GABA_B receptor activity on PDL cells is involved in the modulation of osteoimmunological processes in the periodontium and decides on the initiation versus prevention of host protective mechanisms. This implies anabolic potential for a therapeutic preservation or reestablishment of periodontal tissues under physiological and pathological conditions. In summary, GABA_B receptor modulation in PDL cells might become an important target in immunoinflammatory settings.