Sex- and age-specific regulation of inflammatory processes
Autoimmune diseases, asthma, and other inflammatory disorders have a higher prevalence in women compared to men, often with a more severe course. In addition, men and women respond very differently to certain drugs. In addition, biological age has a major influence on immunological and inflammatory processes. On the one hand, older people suffer more often from silent, chronic inflammation (“inflammaging”) and, on the other hand, the immune system reacts less pronounced to infections and organ damage (“immunosenescence”). Our overall goal is to elucidate the biochemical and molecular mechanisms underlying sex- and age-related differences in the pathophysiology of inflammatory and autoimmune diseases. This will in turn provide insights into optimized, gender-specific or personalized pharmacotherapy (in the sense of “stratified therapy”). At the molecular and cellular level, we focus in particular on bioactive lipid mediators and innate immune cells such as e.g., tissue-associated macrophages. The basis of the project is our discovery of the sex-specific regulation of 5-lipoxygenase (key enzyme in the formation of leukotrienes) by testosterone, which is mediated by the extracellular signal-regulated protein kinase (ERK)-1/2.
Key publications:
Pergola, C., Dodt, G., Rossi, A., Neunhoeffer, E., Lawrenz, B., Hinnak, H., Samuelsson, B., Rådmark, O., Sautebin, L., and Werz, O. (2008) ERK-Mediated Regulation of Leukotriene Biosynthesis by Androgens: A Molecular Basis for Gender Differences in Inflammation and Asthma. Proc Nat. Acad Sci USA, 105,19881-19886
Pace S., Pergola C., Dehm F., Rossi A., Gerstmeier J., Troisi F., Pein H., Schaible A.M., Weinigel C., Rummler S., Northoff H., Laufer S., Maier T.J., Rådmark O., Samuelsson B., Koeberle A., Sautebin L., Werz O. (2017) Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males. J Clin Invest, 127, 3167-3176
Schädel P., Czapka A., Gebert N., Jacobsen I.D., Ori A., Werz O. (2023) Metabololipidomic and proteomic profiling reveals aberrant macrophage activation and interrelated immunomodulatory mediator release during aging. Aging Cell, 22(7), e13856
Research groups:
Carl-Zeiss Forschungsgruppe (Durchbrüche) “IMPULS”