Elevated Foxo3a and Fas‐ligand expression in human periapical granulomas as a potential treatment target

Autor: Keisuke Hatori, Osamu Takeichi, Kazuma Himi, Yurika Toyama, Taiki Miyata, Takahito Tamura, Takeshi Nakamura, Kae Ishii
Rok vydání: 2021
Předmět:
Zdroj: Oral Diseases. 29:1128-1136
ISSN: 1601-0825
1354-523X
Popis: OBJECTIVE Periapical granuloma is a common periodontitis type involving chronic inflammation; however, the efficacy of current therapies is limited. Its molecular pathogenesis also remains obscure. Forkhead box transcription factor class o3a (Foxo3a) and Fas-ligand (FasL) are associated with chronic inflammation. Therefore, in this study, we aimed to clarify the roles of Foxo3a and FasL in periapical granuloma pathophysiology. SUBJECTS AND METHODS Periapical lesions were obtained from patients during endodontic surgery and tooth extraction; those diagnosed with periapical granulomas using haematoxylin and eosin staining were further analysed. Immunohistochemical analysis was performed for Foxo3a and FasL, and real-time polymerase chain reaction was performed for FOXO3A, FASL and interleukin (IL)-1β. Healthy gingival tissues were also examined as controls. RESULTS Neutrophils, lymphocytes and plasma cells in the periapical granulomas, but not healthy tissues, expressed Foxo3a. Dual-colour immunofluorescence imaging revealed Foxo3a and FasL co-expression in leukocytes. FOXO3A, FASL and IL-1β mRNA levels in healthy gingival tissues were significantly lower than those in the periapical granulomas. Additionally, FOXO3A and IL-1β expressions were negatively correlated. CONCLUSIONS Phosphorylated Foxo3a may reduce IL-1β release by inhibiting apoptosis through FasL in periapical periodontitis and prevent exacerbation. Thus, Foxo3a is a potential therapeutic agent for periapical periodontitis.
Databáze: OpenAIRE
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