Rene Lutter

(Principal Investigator), PhD

1978 …2022

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Research interests

Chronic and exaggerated inflammatory responses are key features in asthma and chronic obstructive pulmonary disease (COPD) and are associated with clinical symptoms. Our studies are aimed at identifying molecular and cellular mechanisms that control an inflammatory response and that may be aberrant in asthma and/or COPD. In this context we explore two topics. More recently a third focus has been added, that appears crucial in controlling inflammation in patients with acute respiratory distress syndrome (ARDS)/acute lung injury (ALI).

  1. Inflammatory mediators such as interleukins and chemokines drive an inflammatory response. Most inflammatory mediators are encoded by mRNAs that contain AU-rich elements in their 3’-untranslated region, which targets these mRNAs for rapid degradation and ensures their transient expression. Surprisingly, this AU-rich mediated mRNA decay (AMD) is attenuated relatively easy by various mediators (IL-17, IL-1beta) and conditions (metabolic stress, viral infection), which leads to exaggerated inflammatory mediator production. The molecular machinery involved in AMD is not clear yet but involves a number of AU-binding proteins and possibly also microRNAs. We aim to identify the constituents that facilitate degradation of a number of mRNA (encoding IL-6, IL-8, VEGF and IP-10) and assess the effect of IL-17 on this molecular machinery. In addition we wil analyze this machinery in bronchial epithelial cells from patients with asthma and COPD.
  2. Indoleamine 2,3-dioxygenase (IDO) is an inducible tryptophan-catabolizing enzyme, which has anti-microbial properties and has been implicated in blocking T cell activation by promoting apoptosis and halting cell cycle progression. Our studies indicate that IDO activity attenuates not only T cell numbers and function, but also that of granulocytes and macrophages. In fact, we propose that IDO promotes resolution of inflammation. So, when a microbial challenge occurs parallel to a profound IDO activity, the challenge is not controlled well. IDO is also expressed in granuloma, and currently we are determining its contribution to the function of granuloma in chronic granulomatous disease, tuberculosis and sarcoidosis.
  3. Earlier studies have indicated that angiotensin-converting enzyme (ACE) mediates the inflammatory response in lungs of experimental ARDS/ALI. Our recent studies have shown that ARDS in animals that were exposed to LPS, as a model of lung infection, is dependent on ACE as well as ACE2. ACE2, a recently recognized enzyme, is shed in LPS exposed lungs, as a consequence of which there is no or reduced generation of angiotensin 1-7. The addition of a stable form of angiotensin 1-7 to a large extent prevents the development of inflammation. Currently, we aim to clarify the underlying mechanism and are exploring this stable angiotensin 1-7 as a treatment modality.

The findings of these studies may also be relevant to other chronic inflammatory diseases.

 

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

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