Targeting lysine acetylation in inflammatory lung diseases

Thea van den Bosch

Research output: ThesisThesis fully internal (DIV)

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Abstract

Inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are still a major problem. For a group of patients the current therapy does not work, or does not work effectively, and there are many side effects. Therefore, there is a need for new drugs that work in a different way.
In our research, we focused on two new groups of enzymes. We looked at the histone acetyltranferases (HATs) and histone deacetylases (HDACs). It is becoming increasingly clear that these enzymes play a role in inflammation. Substances that inhibit these enzymes can potentially be used as new drugs. In order to achieve this goal, the effects of the inhibition of these enzymes on inflammatory responses must be specified in detail in disease models.
In our research, we focused on a number of specific molecular processes involved in inflammation. It was found that inhibitors of both HATs and HDACs have an inhibitory effect on these processes, suggesting that it is possible to reduce inflammation with these substances. The most promising results were achieved with a selective inhibitor of specific subtypes of HDAC enzymes. We observed that this inhibitor has an anti-inflammatory effect in immune cells and lung tissue. In a disease model for COPD, the inhibitor strongly reduced the number of immune cells in the lungs, which clearly indicates inhibition of the inflammatory process. This shows that further study of this type inhibitors for future applications in inflammatory diseases is promising.
Translated title of the contributionHet targetten van lysine acetylering bij inflammatoire longziekten
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Groningen
Supervisors/Advisors
  • Dekker, Frank, Supervisor
  • Haisma, Hidde, Supervisor
Award date16-Jun-2017
Place of Publication[Groningen]
Publisher
Print ISBNs978-90-367-9816-7
Electronic ISBNs978-90-367-9815-0
Publication statusPublished - 2017

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