Abstract
Necroptosis, a form of programmed lytic cell death, has emerged as a driving factor in the pathogenesis of acute lung injury. One specific inflammatory mediator that is of interest is interferon-γ (IFN-γ). Our laboratory has reported that IFN-γ is the most potent enhancer of necroptosis in primary lung epithelial cells and macrophages by upregulating MLKL expression. How IFN-γ enhances necroptosis and MLKL upregulation is currently unknown. In this research, we utilized multiple approaches to study the potential molecular mechanisms of IFN-γ promoted necroptosis in macrophages. We found that MLKL and ZBP1 are significantly upregulated by IFN-γ through an unknown pathway downstream of Jak kinase. The phosphorylation of RIPK1, RIPK3, and MLKL was accelerated by pretreatment with IFN-γ upon induction of necroptosis. Whereas IFN-γ did not affect the ubiquitination of MLKL. Moreover, we found that necroptosis caused MLKL degradation or loss in the membrane fraction, which was prevented by IFN-γ treatment. This effect may be a critical mechanism responsible for the enhanced necroptosis observed in IFN-γ pretreated macrophages.
Date of publication
2023
Document Type
Thesis
Language
english
Persistent identifier
http://hdl.handle.net/10950/4272
Committee members
Dr. Hua Tang, Dr. Pierre Neuenschwander, Dr. Guohua Yi, Dr. Guoqing Qian, Dr. Ali Azghani
Degree
Master of Science in Biotechnology
Recommended Citation
Vogt, Meghan R., "THE MOLECULAR MECHANISMS OF IFN-γ PROMOTED NECROPTOSIS IN MACROPHAGES" (2023). Biotechnology Theses. Paper 15.
http://hdl.handle.net/10950/4272