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Decisions in metabolic inflammation of the liver: Adhesive interactions involved in leukocyte retention and resolution of inflammation in metabolic-inflammatory liver disease

Objective

Resolution of acute inflammation, involving limiting further leukocyte recruitment, apoptosis and clearance
of inflammatory cells via macrophages as well as egress of the inflammatory cells, is operative in acute
inflammation but dysfunctional in chronic inflammatory disease. In the latter scenario, the retention and
activation of leukocytes in the inflamed tissue linked with failure to resolve inflammation contributes to
perpetuation of organ damage and loss of homeostasis. Interestingly, persistent inflammation in insulintarget
organs, such as the adipose tissue and the liver in the context of obesity significantly contributes to
development of insulin resistance (IR), diabetes and non-alcoholic fatty liver disease (NAFLD). So far,
investigations have mainly addressed obesity-related inflammatory mechanisms in the AT and rather less in
other metabolic organs, e.g. the liver. Therefore, the aims of this proposal are: (i) To characterize in the
context of obesity-related metabolic disease novel processes mediating inflammatory cell retention,
especially in the liver. In this context, we will also address the novel hypothesis that adhesive interactions of
inflammatory cells (with e.g. parenchymal cells) in the metabolically challenged environment of obese
organs may activate them via alterations in their cellular metabolism, thereby contributing to perpetuation of
inflammation. (ii) To understand resolution of inflammation including inflammatory cell egress from
metabolic organs, especially from the liver in metabolic-inflammatory disease. To this end, we will also
utilize models of acute inflammation, which is capable to resolve, in order to understand resolution principles
and apply them to non-resolving metabolic-inflammatory disease. In this regard, we will also assess the
therapeutic potential of novel inflammation-modulating factors identified by our lab.

Host institution

TECHNISCHE UNIVERSITAET DRESDEN
Net EU contribution
€ 1 953 250,00
Address
HELMHOLTZSTRASSE 10
01069 Dresden
Germany

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Region
Sachsen Dresden Dresden, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 953 250,00

Beneficiaries (1)