Investigating the mechanism of activation by inflammatory signaling molecules S100A9 and lipopolysaccharides

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Date

2021

Authors

Murawsky, Hannah

Journal Title

Journal ISSN

Volume Title

Publisher

University of Oregon

Abstract

Inflammation is the most common cause of death worldwide. Mediated by the innate immune system, inflammation serves as one of the first lines of defense against infection and injury. However, when this natural and healthy response runs amok, it can cause and exacerbate many diseases. The innate immune receptor Toll-like Receptor 4 (TLR4), along with its cofactors, MD-2 and CD14, activates inflammation in response to external and internal danger signals. TLR4 induced inflammation is implicated in sepsis and many other inflammatory disease states. Despite the significance of this receptor complex for human health, much is yet to be understood regarding the biochemical mechanism by which it recognizes danger signals. In particular, the role of the cofactor CD14 is well understood for external danger signals, but its role in internal danger signal recognition is poorly understood. By introducing mutations to CD14 and measuring their effect on TLR4 induced inflammation, I have determined the importance of specific amino acids and regions of CD14 involved in activation by internal danger signals.

Description

42 pages

Keywords

Biochemistry, Molecular Biology, Immunology, Inflammation, Toll-like Receptor

Citation