講演情報
[P-102（E）]Stage-Dependent and Analog-Specific Regulation of Inflammatory Signaling by Prostacyclin Analogs in Human Dental Pulp Fibroblasts
*Yuancan Chen1, Akiyo Kawamoto1, Kazuya Takahashi1 (1. Department of Geriatric Dentistry, Osaka Dental University)
[Objective]
Inflammation is a key factor in the progression of pulpitis and directly affects pulp vitality and clinical outcomes, particularly in prosthodontic treatments. Tooth preparation for restorations inevitably imposes mechanical and chemical stimuli on the dental pulp, which may trigger inflammatory responses and compromise pulp vitality. Therefore, controlling pulp inflammation is critical for improving the long-term prognosis of vital teeth following prosthodontic treatment1. Prostacyclin (PGI2) analogs are known to regulate inflammatory responses2; however, their effects on inflammatory signaling pathways and cytokine production in human dental pulp fibroblasts (HDPFs) remain unclear. This study aimed to compare the anti-inflammatory effects of different PGI2 analogs on LPS-induced inflammation in HDPFs and to elucidate the underlying signaling mechanisms.
[Methods]
HDPFs were stimulated with lipopolysaccharide (LPS) to induce inflammation, which was assessed by measuring cytokine IL-6 and IL-8 production using enzyme-linked immunosorbent assay (ELISA) and by western blot analysis of MAPK (ERK and p38) and NF-kappaB (p65) inflammatory signaling pathways. Following LPS stimulation, HDPFs were treated with PGI2 analogs (treprostinil, iloprost, and epoprostenol). The effects of each PGI2 analog were evaluated based on changes in cytokine production, inflammatory signaling, and prostacyclin-related PKA-CREB signaling.
[Results and Discussion]
LPS stimulation markedly increased phosphorylation of ERK, p38, and p65 and enhanced IL-6 and IL-8 production in HDPFs. Treprostinil significantly suppressed both IL-6 and IL-8 expression, whereas iloprost reduced IL-8 without affecting IL-6 levels. In contrast, epoprostenol further increased IL-6 and IL-8 expression under the same conditions. Western blot analysis demonstrated that treprostinil effectively attenuated LPS-induced phosphorylation of ERK, p38, and p65. Furthermore, treprostinil reduced LPS-induced increases in PKA and CREB protein expression. Collectively, treprostinil showed the strongest anti-inflammatory effects, iloprost exhibited moderate inhibitory activity, and epoprostenol did not exert anti-inflammatory effects in LPS-stimulated HDPFs.
[References]
1. Lim ZE, Duncan HF, Moorthy A, et al. Minimally invasive selective caries removal: a clinical guide. Br Dent J. 2023;234.
2. Lai YC, Potoka KC, Champion HC, et al. Pulmonary arterial hypertension: the clinical syndrome. Circ Res. 2014;115.
Inflammation is a key factor in the progression of pulpitis and directly affects pulp vitality and clinical outcomes, particularly in prosthodontic treatments. Tooth preparation for restorations inevitably imposes mechanical and chemical stimuli on the dental pulp, which may trigger inflammatory responses and compromise pulp vitality. Therefore, controlling pulp inflammation is critical for improving the long-term prognosis of vital teeth following prosthodontic treatment1. Prostacyclin (PGI2) analogs are known to regulate inflammatory responses2; however, their effects on inflammatory signaling pathways and cytokine production in human dental pulp fibroblasts (HDPFs) remain unclear. This study aimed to compare the anti-inflammatory effects of different PGI2 analogs on LPS-induced inflammation in HDPFs and to elucidate the underlying signaling mechanisms.
[Methods]
HDPFs were stimulated with lipopolysaccharide (LPS) to induce inflammation, which was assessed by measuring cytokine IL-6 and IL-8 production using enzyme-linked immunosorbent assay (ELISA) and by western blot analysis of MAPK (ERK and p38) and NF-kappaB (p65) inflammatory signaling pathways. Following LPS stimulation, HDPFs were treated with PGI2 analogs (treprostinil, iloprost, and epoprostenol). The effects of each PGI2 analog were evaluated based on changes in cytokine production, inflammatory signaling, and prostacyclin-related PKA-CREB signaling.
[Results and Discussion]
LPS stimulation markedly increased phosphorylation of ERK, p38, and p65 and enhanced IL-6 and IL-8 production in HDPFs. Treprostinil significantly suppressed both IL-6 and IL-8 expression, whereas iloprost reduced IL-8 without affecting IL-6 levels. In contrast, epoprostenol further increased IL-6 and IL-8 expression under the same conditions. Western blot analysis demonstrated that treprostinil effectively attenuated LPS-induced phosphorylation of ERK, p38, and p65. Furthermore, treprostinil reduced LPS-induced increases in PKA and CREB protein expression. Collectively, treprostinil showed the strongest anti-inflammatory effects, iloprost exhibited moderate inhibitory activity, and epoprostenol did not exert anti-inflammatory effects in LPS-stimulated HDPFs.
[References]
1. Lim ZE, Duncan HF, Moorthy A, et al. Minimally invasive selective caries removal: a clinical guide. Br Dent J. 2023;234.
2. Lai YC, Potoka KC, Champion HC, et al. Pulmonary arterial hypertension: the clinical syndrome. Circ Res. 2014;115.