75 Views

OR23 - Future Targeted Precision Treatment Strategies for Apical Periodontitis: Assessing Expression of Interferon Regulatory Factor 8 in Monocytes After Pharmacological Modulation of Autophagy

Wednesday, May 3, 2023

2:30 PM – 2:45 PM CT

Location: E353A (Level 3)

Presenter(s)

Mansoor Safder, D.D.S.

Endodontics Resident
University of Texas at Houston
Houston, Texas

Disclosure information not submitted.

Co-Author(s)

Zhen Shen, D.M.D., M.S.D., Ph.D.

Clinical Assistant Professor
University of Texas at Houston
UTHealth School of Dentistry at Houston
Houston, Texas

Disclosure information not submitted.
JC

John Chiorini, Ph.D.

Senior investigator
University of Alberta
bethesda, Maryland

Disclosure information not submitted.
Leticia Chaves de Souza, D.D.S., M.S., PhD

Resident
University of Texas at Houston
Houston, Texas

Disclosure information not submitted.
TC

Tracy M. Clark, D.D.S.

Assistant Professor
University of Texas at Houston
Houston, Texas

Disclosure information not submitted.
Renato M. Silva, D.D.S., M.S., Ph.D.

Professor
University of Pittsburgh
Pittsburgh, Pennsylvania

Disclosure information not submitted.
Ariadne Letra, D.D.S., M.S., Ph.D.

Professor
University of Pittsburgh
Pittsburgh, Pennsylvania

Disclosure information not submitted.
Timothy C. Kirkpatrick, D.D.S.

Program Director
University of Texas at Houston
Houston, Texas

Disclosure information not submitted.

Microbial infection of the dental pulp and its propagation through the root canal system leads to the development of apical periodontitis that involves various types of immune cells, such as neutrophils, macrophages, and lymphocytes. Autophagy plays a critical role in inflammation by modulating the homeostasis and development of these cells. Recently, interferon regulatory factor 8 (IRF8) has been shown to be essential in strengthening the early immune response during infection by stimulating antimicrobial defenses in macrophages and monocytes. The aim of this study was to investigate the relationship between IRF8 and the regulation of autophagy in inflammation. Autophagy was induced and inhibited in human leukemia monocytic cell line THP-1 via the treatment of Rapamycin (mTOR inhibitor) and 3-Methyladenine (PI3K inhibitor), respectively. The cytotoxicity and proliferation of the cells were assessed under these treatments. Changes in the expression of IRF8 and other key markers of autophagy were measured at the transcript and protein levels via quantitative real-time polymerase chain reaction and Western Blot. IRF8, NBR1, WDR45, and ULK1 (P < 0.05, one-way ANOVA) were significantly upregulated upon induction of autophagy. Moreover, RNA sequencing was conducted in THP-1-treated cells, bioinformatics and statistical analyses were performed, and the differentially expressed genes, especially in IRF8-related pathways, were identified. In conclusion, IRF8 and its related pathways are associated with the activation of autophagy and may be developed into a potential therapeutic target and used as an adjunct therapy in the treatment of apical periodontitis.