Cannabinoid type-2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL-1β stimulated primary human periodontal ligament fibroblasts
| Autor: | Sahar S. Alghamdi, David A. Tipton, Mustafa Kh. Dabbous, Ammaar H. Abidi, Suni M. Mustafa, Bob M. Moore |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Periodontal Ligament Polyunsaturated Alkamides medicine.medical_treatment Inflammation Arachidonic Acids Pharmacology Receptor Cannabinoid CB2 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Cannabinoid receptor type 2 Inverse agonist Humans Receptor Cells Cultured Cannabinoids Interleukin-18 030206 dentistry Anandamide Fibroblasts 030104 developmental biology Cytokine chemistry Periodontics Cannabinoid medicine.symptom Endocannabinoids |
| Zdroj: | Journal of periodontal researchREFERENCES. 55(5) |
| ISSN: | 1600-0765 |
| Popis: | Objective The aim of this study is to understand the role of cannabinoid type 2 receptor (CB2R) during periodontal inflammation and to identify anti-inflammatory agents for the development of drugs to treat periodontitis (PD). Background Cannabinoid type 2 receptor is found in periodontal tissue at sites of inflammation/infection. Our previous study demonstrated anti-inflammatory responses in human periodontal ligament fibroblasts (hPDLFs) via CB2R ligands. Methods Anandamide (AEA), HU-308 (agonist), and SMM-189 (inverse agonist) were tested for effects on IL-1β-stimulated cytokines, chemokines, and angiogenic and vascular markers expressed by hPDLFs using Mesoscale Discovery V-Plex Kits. Signal transduction pathways (p-c-Jun, p-ERK, p-p-38, p-JNK, p-CREB, and p-NF-kB) were investigated using Cisbio HTRF kits. ACTOne and Tango™ -BLA functional assays were used to measure cyclic AMP (cAMP) and β-arrestin activity. Results IL-1β stimulated hPDLF production of 18/39 analytes, which were downregulated by the CB2R agonist and the inverse agonist. AEA exhibited pro-inflammatory and anti-inflammatory effects. IL-1β increased phosphoproteins within the first hour except p-JNK. CB2R ligands attenuated p-p38 and p-NFĸB, but a late rise in p-38 was seen with HU-308. As p-ERK levels declined, a significant increase in p-ERK was observed later in the time course by synthetic CB2R ligands. P-JNK was significantly affected by SMM-189 only, while p-CREB was elevated significantly by CB2R ligands at 180 minutes. HU-308 affected both cAMP and β-arrestin pathway. SMM-189 only stimulated cAMP. Conclusion The findings that CB2R agonist and inverse agonist may potentially regulate inflammation suggest that development of CB2R therapeutics could improve on current treatments for PD and other oral inflammatory pathologies. |
| Databáze: | OpenAIRE |
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