GABABReceptors as Modulating Target for Inflammatory Responses of the Periodontal Ligament.
PDL cells express GABAB1and GABAB2receptors, 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 GABABreceptors in immunomodulation regarding activation of proregenerative versus proinflammatory mechanisms. Human PDL cells were exposed to GABA and/or GABABreceptor 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. GABABreceptor 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. GABABreceptor 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, GABABreceptor modulation in PDL cells might become an important target in immunoinflammatory settings.
Department of Orthodontics, Medical Faculty, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany. konermann@uni-bonn.de.
Anna
A
Konermann
Forsyth Institute, 245 First St, Cambridge, MA, 02142, USA.
Thomas
T
Van Dyke
Forsyth Institute, 245 First St, Cambridge, MA, 02142, USA.
Alpdogan
A
Kantarci
Department of Orthodontics, Medical Faculty, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany.
Andreas
A
Jäger
D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008903:Minerals / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010513:Periodontal Ligament / Q000378:metabolism* / Q000473:pathology*; D018080:Receptors, GABA-B / Q000378:metabolism*
D016207:Cytokines; D008903:Minerals; D016328:NF-kappa B; D018080:Receptors, GABA-B
Inflammation; Neurotransmitter; Periodontal ligament cells; Periodontal pathophysiology; γ-Aminobutyric acid (GABA) B receptors