Effect of interleukin-1β on ghrelin receptor in periodontal cells
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Periodontopathogens induce immunoinflammatory responses characterized by the release of inflammatory mediators, e.g., interleukin (IL)-1β, IL-6, and IL-8. Ghrelin (GHRL) is an appetite hormone which mediates its effect via the functional receptor GHS-R1a. This study was to examine the effect of an inflammatory insult on GHS-R1a in human periodontal cells.
Materials and methods
Periodontal ligament (PDL) cells and gingival fibroblasts (HGFs) were exposed to IL-1β in the presence and absence of GHRL. Cells were also pre-incubated with specific inhibitors of NF-κB or MEK1/MEK2 signaling. Gene expression of GHS-R1a and proinflammatory mediators was assessed by real-time PCR, GHS-R1 protein level by immunocytochemistry, and NF-κB nuclear translocation by immunofluorescence.
IL-1β increased significantly the GHS-R1a expression in both cell types in a dose-dependent manner. The stimulatory effect of IL-1β involved the NF-κB and MAPK pathways. Exposure of cells to IL-1β also resulted in an increased production of GHS-R1 protein in both cell types. Furthermore, GHRL counteracted significantly the stimulatory actions of IL-1β on IL-6 and IL-8 in PDL cells.
This study demonstrates for the first time that IL-1β upregulates the functional ghrelin receptor in periodontal fibroblastic cells. Moreover, these results further support the assumption that the GHRL/GHS-R system exerts anti-inflammatory effects. Therefore, the upregulation of ghrelin receptor in periodontal cells in response to an inflammatory stimulus may represent a negative feedback mechanism to attenuate the initial inflammatory process in periodontal diseases.
The anti-inflammatory GHRL/GHS-R system may serve as a promising target for the prevention and therapy of periodontal diseases.
KeywordsGhrelin receptor Ghrelin Gingival fibroblast Periodontal ligament cell Interleukin-1β Periodontitis
The authors would like to thank Prof. Heiko Spallek, Ms. Ramona Menden, and Ms. Silke van Dyck for their valuable support. This study was supported by the Medical Faculty of the University of Bonn and the University of Sydney.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.
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