Örebro Studies in Medicine 224 I
ÖREBRO 2020 2020M
AD
EL
ENE
L
IND
KV
IS
T
IL-6 f
am
ily s
ig
na
lling i
n e
nd
oth
eli
al ce
lls a
nd p
la
te
le
ts
madelene lindkvist received her Bachelor of Science degree in Biomedicine in 2012 and Master of Science de-gree in Medicine in 2014, both from Örebro University. In 2014, Madelene started her PhD studies at the Cardiovas-cular Research Centre (CVRC) at the School of Medical Sciences, Örebro University.
The vessel wall is covered by a monolayer of endothelial cells, creating a barrier to the circulating blood. Endothelial cells have important functions in regulation of vessel tension and inflammation. Furthermore, endothelium-derived vasodilators prevent our smallest blood cells, platelets, to aggregate in the circulation. The main physiological role of platelets is to protect us from bleeding by creating aggregates at sites of injury. Platelets is also increasingly recognised as mediators in acute inflam-mation. The focus of this thesis has been to study the impact of inflammatory cytokines in the interleukin (IL)-6 family, also called glycoprotein (gp) 130 signalling cytokines, on endothelial cells and platelets. IL-6 is associated to both pro- and anti-inflammatory outcomes, however, the underlying mole-cular mechanisms for these pleiotropic effects is not well known. Increased knowledge in this field will facilitate improvement of current therapeutical strategies towards inflammatory cytokines.
In this thesis, the impact of various gp130 signalling cytokines on en-dothelial cells revealed differences and similarities in intracellular signalling, gene expression and protein release. In platelets, IL-6 was shown to inhibit epinephrine-induced platelet aggregation when combined with the soluble IL-6 receptor. Furthermore, this thesis revealed inter-individual differences in platelet reactivity towards activators and the inhibitor nitric oxide (NO). Individuals with more NO-sensitive platelets showed greater capacity of vasodilation, indicating a connection between endothelial function and platelet inhibition.
issn 1652-4063 isbn 978-91-7529-359-2