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Pro-inflammatory cytokine regulation by the immunomodulatory protein p33

Anders, Emma (2017) MOBT01 20162
Degree Projects in Molecular Biology
Popular Abstract
p33 as a potential novel therapeutic target in inflammatory diseases

Inflammation is a condition usually triggered by infection of invading pathogens such as bacteria or viruses in the body. This invasion is quickly recognized by specific receptors localized on the membrane of cells, ready to sense these so called “danger” signals or foreign material. These receptors are part of the innate immunity which is the initiating event in the inflammation. It is characterized by the cellular uptake and degradation of the invading pathogen by specialized immune cells and subsequent activation of the adaptive immunity. The adaptive immunity is more specific and has an immunological memory which enables and enhances the response at future... (More)
p33 as a potential novel therapeutic target in inflammatory diseases

Inflammation is a condition usually triggered by infection of invading pathogens such as bacteria or viruses in the body. This invasion is quickly recognized by specific receptors localized on the membrane of cells, ready to sense these so called “danger” signals or foreign material. These receptors are part of the innate immunity which is the initiating event in the inflammation. It is characterized by the cellular uptake and degradation of the invading pathogen by specialized immune cells and subsequent activation of the adaptive immunity. The adaptive immunity is more specific and has an immunological memory which enables and enhances the response at future encounters with the same pathogen. An important event in the initiating steps of inflammation is the cellular secretion of signaling molecules called chemokines, which direct the white blood cells to the site of infection to fight against the intruder. An inflammatory response must be tightly regulated; it has to be sufficient to eradicate the invader but it must also be controlled to prevent the development of a chronic inflammation. The body has several mechanisms for this purpose, and one of these may be a cellular protein called p33 which is highly expressed during inflammation.

p33
p33 is a multifunctional protein expressed in all compartments of all cells, except in the red blood cells and it is involved in innate immunity. Three p33 monomers assemble to form a trimeric doughnut-shaped structure which has one side much more negatively charged than the other. p33 acts as a receptor for many different ligands involved in inflammatory responses and this polarity seem to be crucial for its binding function. p33 is an essential, evolutionary conserved protein between different species, and induced deletion of the gene has shown embryonic failure in mice, further indicating its importance.

Project description and results
Here, in this project, we have investigated the role of p33 in regulating the expression of different pro-inflammatory cytokines in vitro, in two different human cell types. This was done by inhibition of p33 expression, followed by evaluation methods of both gene and protein level of several potential targets. We have localized p33 in the cells and found that the protein may act both pro-inflammatory and anti-inflammatory, depending on the cell type. We also have novel findings of p33 interacting and binding with one specific important chemokine involved in the initial recruitment of white blood cells to a site of infection.

This project has served to increase the understanding of p33 as a regulator of inflammation. Due to its repertoire of functions and its involvement in inflammatory responses, p33 is suggested to be a new potential therapeutic target for treatment of several inflammatory diseases.


Supervisors: Dr. Daniel Svensson, Prof. Bengt-Olof Nilsson
Vascular Physiology
Department of Experimental Medical Science, Faculty of Medicine
Master´s Degree Project in Molecular Biology 60 credits 2017
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Anders, Emma
supervisor
organization
course
MOBT01 20162
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8925263
date added to LUP
2017-09-11 11:53:20
date last changed
2017-09-11 11:53:20
@misc{8925263,
  author       = {Anders, Emma},
  language     = {eng},
  note         = {Student Paper},
  title        = {Pro-inflammatory cytokine regulation by the immunomodulatory protein p33},
  year         = {2017},
}