Density dependent regulation of inflammatory responses in macrophages

Journal article

Thesis (Ph.D.)--Michigan State University. Biomedical Engineering - Doctor of Philosophy, 2025Many conditions of chronic inflammation, such as ulcerative colitis, predispose an individual to developing cancer. The predisposition of chronically inflamed tissue to neoplasia and malignancy is referred to as immunocarcinogenesis. Colitis is characterized by relapsing episodes of inflammation and ulceration in the colonic mucosa. Macrophages play an important role in regulating the immune response in colitis, and secrete proinflammatory factors that may promote colitis-associated cancer. Extracellular vesicles (EVs) have been shown to mediate colitis and colon cancer progression, and there is accumulating evidence suggesting that the activation states of macrophages influence EV secretion and signaling effects in inflammation and cancer. Macrophages in the ulcerated colonic submucosa are exposed to increased levels of bacterial endotoxins, so we sought to model EVs from colitis in culture using EVs from lipopolysaccharide (LPS)-activated macrophages. To investigate the impact of EVs from macrophages on mediating colitis-associated cancer, we characterized EVs from LPS-activated macrophages, treated colon cells and tumors with isolated macrophage EVs, and analyzed the inflammatory and pro-tumorigenic effects in vitro and in vivo. Our results provide evidence that EVs released from LPS-activated macrophages increase inflammation in the colonic epithelium, can promote cell growth, lead to anchorage-independent growth, induce pro-tumorigenic protein expression in transformed cells, and significantly alter the local immune environment. These findings suggest that macrophage-derived EVs may serve as key mediators between colonic inflammation and cancer development, and identify specific EV proteins as potential therapeutic targets to interrupt the progression of colitis-associated malignancy.Description based on online resource. Title from PDF t.p. (Michigan State University Fedora Repository, viewed ).Includes bibliographical references

Authors: Vaughan-Jackson, A; Stodolak, S; Ebrahimi, KH; Johnson, E; Reardon, PK

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Frontiers Media
• Journal: Frontiers in Immunology
• Volume: 13
• Pages: 895488-895488
• Article number: 895488
• Publication date: 2022-12-16
• DOI: 10.3389/fimmu.2022.895488
• EISSN: 1664-3224
• ISSN: 1664-3224
• Language: English
• Keywords: In vitro; Immunology; Inflammatory response; Biology; Cell biology; Medicine; Biochemistry; Inflammation; Macrophage