Dissertation/Thesis Abstract

Complement Protein C1q Modulates Macrophage NLRP3 Inflammasome Activation
by Manughian-Peter, Ayla, M.S., California State University, Long Beach, 2018, 53; 10690316
Abstract (Summary)

Atherosclerosis disease pathology is largely influenced by immune cells infiltrating the arteries, particularly macrophages. Pro-inflammatory macrophages secrete cytokines and enzymes that contribute to plaque rupture and serious medical complications. Typically, immune proteins from the complement system also exacerbate disease pathology. Interestingly, novel non-complement roles of complement activator C1q suggest a protective role via polarization of macrophages towards an anti-inflammatory phenotype. Differential transcriptomic analysis in human macrophages suggests that C1q may influence macrophage inflammatory phenotype by modulating the levels of components of the NLRP3 inflammasome, a protein complex responsible for activation of inflammatory cytokines IL-1β and IL-18. My data suggest that when bound to oxidized LDL (oxLDL), C1q downregulates NLRP3 inflammasome related genes and reduces inflammasome activity, leading to a reduction in IL-1β secretion from pro-inflammatory macrophages. However, these effects appear to be target-specific, as this reduction in inflammasome activity was not observed when C1q was bound to E. coli bioparticles. This indicates that this non-complement role of C1q may be important in dampening inflammation in the early atherosclerotic lesion. Discerning the molecular pathways that regulate inflammatory states of macrophages can contribute to the development of therapeutics for chronic inflammatory illnesses.

Indexing (document details)
Advisor: Fraser, Deborah A.
Commitee: Tsai, Houng-Wei, Zhang, Mason
School: California State University, Long Beach
Department: Biological Sciences
School Location: United States -- California
Source: MAI 57/05M(E), Masters Abstracts International
Source Type: DISSERTATION
Subjects: Biology
Keywords:
Publication Number: 10690316
ISBN: 9780355715545
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