82 Chapter 3 use of self-propagating cells, which was necessary to obtain a sufficient protein yield for proteomics analysis and metabolite production. However, it should be noted that our model does not accurately replicate the in vivo environment as it only represents a single immune cell population and lacks the complex matrix in which the cells reside. Nonetheless, this model holds potential for investigating the influence of lysine deacetylation on diseases regulated by macrophages and exploring therapeutic interventions. In conclusion, we found that inhibition of protein deacetylation and notably of KDAC3 attenuates activation of LPS-stimulated alveolar-like macrophages but has surprisingly little effect on macrophage metabolism. Other inhibitory mechanisms, such as a reduced level of protein ubiquitination, may open new avenues for the treatment of diseases characterized by chronic inflammation, like COPD, that do not respond well to corticosteroids. CONFLICT OF INTEREST The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AUTHORS CONTRIBUTION SR, MK, NG, RB, and BM conceived and designed the set-up of the manuscript. SR drafted the manuscript and prepared figures. SR, RB, and BM edited and revised the manuscript. SR, JC, AG, and JH performed experiments and all approved the final version. ACKNOWLEDGMENTS AND FUNDING The Noordelijke CARA stichting is gratefully acknowledged for funding part of the work described (project number 134426). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 754425.
RkJQdWJsaXNoZXIy MTk4NDMw