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Activation of NLRP3 inflammasome leads to the differential secretion of interleukins 1*/18 possibly linked to pyroptosis in THP-1 cells

Organisms are constantly exposed to microorganisms, some of which can cause disease, and yet, sickness only rarely occurs. Upon infection, the immune system is mobilized to eliminate the threat and re-establish homeostasis. The innate immune system, or “first line of defense”, is responsible for detecting infection and subsequently initiating inflammation. An important mediator of this process is the NLRP3 inflammasome, a molecular hub that coordinates the propagation of the immune response. Specifically, through the secretion of interleukins 1 and 18. These structurally related proteins are known to be secreted via unconventional pathways, however, the specificity of this matter remains inconclusive. One form of secretion suggested was “pyroptosis”, a form of cell death intended to enhance inflammation. The aim of this project was to quantify the secretion of structurally related interleukins-1/18 and evaluate the possible correlation with cell death over time. Samples were collected, interleukin release was quantified using sandwich ELISA and cell viability of stimulated cells was measured using the PrestoBlue assay. During prolonged inflammasome activation, IL-1 and IL-18 showed differences in their patterns of secretion and regulation. IL-1 was eventually downregulated whilst IL-18 maintained a constant increase over time. Strikingly, cell viability remained unchanged over the course of the experiment, demonstrating that pyroptosis is dispensable to the secretion of interleukins 1 and 18. Ultimately, the study of the relationship shared between these processes not only explains how immunity is founded, but also, uncovers the truths behind pathogenesis, how to prevent it and potentially find a cure for certain diseases.

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:his-18634
Date January 2020
CreatorsDamiani, Jana
PublisherHögskolan i Skövde, Institutionen för biovetenskap
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeStudent thesis, info:eu-repo/semantics/bachelorThesis, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess

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