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Dissertation/Thesis Abstract

Runx3-Mediated Suppression of Macrophage Inflammatory Activation
by Kleam, Joshua Kenneth, M.S., The University of Texas Health Science Center at Tyler, 2020, 40; 28001246
Abstract (Summary)

Macrophages including the tissue resident and monocyte-derived macrophages are crucial for host innate immune defense against viral and bacterial infections. However, this innate immune response must be tightly controlled to minimize immunopathology. Studies have demonstrated that the activated macrophages produce high levels of pro-inflammatory chemokines, cytokines as well as cell death-inducing ligands, greatly contributing to tissue injury, morbidity, and mortality. To identify the crucial regulators of macrophage inflammatory activation, we investigated the role of Runx3 in the regulation of macrophage subtypes and functions. We hence prepared bone marrow-derived macrophages from an inducible Runx3 general knockout (KO) mouse model and investigated the effects of Runx3 KO on macrophage M1/M2 subtype formation, phagocytosis/uptake, and the production of chemokines and cytokines. We found that Runx3 KO promoted macrophage M1 subtype but decreased M2 subtype formation in response to double-stranded RNA (dsRNA) that is a viral pathogen associated molecular pattern. Interestingly, Runx3 KO also markedly augmented macrophage production of pro-inflammatory chemokines and cytokines in response to dsRNA. Collectively, these findings suggest that Runx3 may function to suppress macrophage inflammatory activation by promoting macrophage M1 to M2 phenotype transition and suppressing cytokine and chemokine production to facilitate disease resolution.

Indexing (document details)
Advisor: Tang, Hua, Boggaram, Vijayakumar
Commitee: Mulik, Sachin, Samten, Buka
School: The University of Texas Health Science Center at Tyler
Department: Cellular and Molecular Biology
School Location: United States -- Texas
Source: MAI 82/1(E), Masters Abstracts International
Subjects: Immunology, Biochemistry, Biology
Keywords: Immunology, Macrophage, Runx3
Publication Number: 28001246
ISBN: 9798662403888
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