- Immune cells in cancer
- Peroxisome Proliferator-Activated Receptors
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Cholesterol and Lipid Metabolism
- Epigenetics and DNA Methylation
- interferon and immune responses
- Signaling Pathways in Disease
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Phagocytosis and Immune Regulation
- Advanced Glycation End Products research
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- Adenosine and Purinergic Signaling
- Liver Disease Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Calcium signaling and nucleotide metabolism
- Redox biology and oxidative stress
- Metabolomics and Mass Spectrometry Studies
- Protein Kinase Regulation and GTPase Signaling
- Ubiquitin and proteasome pathways
Goethe University Frankfurt
2015-2024
University Hospital Frankfurt
2021
Society of Interventional Radiology
2015
Institute of Biochemistry
2015
Universidade de São Paulo
2011
Goethe Institute
2010
University of Konstanz
2000-2002
Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation promote tissue repair. While alternatively activated macrophages (AAMs), also referred as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute the suppression inflammatory responses play a pivotal role in wound healing, contemporaneous exposure apoptotic cells (ACs) potentiates expression repair genes. Given that liver X receptors (LXRs), which coordinate sterol...
Compared to cancer cells, macrophages are inert lipid peroxidation-triggered, iron-dependent cell death known as ferroptosis. Mechanisms underlying macrophage resistance towards ferroptosis largely obscure. Here, we show that human primary respond RSL3, a ferroptosis-inducing inhibitor of glutathione peroxidase 4, by upregulating mRNA expression the iron transporter ferroportin. RSL3 induces peroxidation, and both, peroxidation well ferroportin induction were attenuated liproxstatin-1, an...
The interaction of protein serine/threonine phosphatase calcineurin (CaN) with superoxide and hydrogen peroxide was investigated. Superoxide specifically inhibited activity CaN toward RII (DLDVPIPGRFDRRVSVAAE) phosphopeptide in tissue cell homogenates as well the enzyme purified under reducing conditions. Hydrogen an effective inhibitor at concentrations several orders magnitude higher than superoxide. Inhibition by calcium/calmodulin-dependent. Nitric oxide (NO) antagonized action on CaN....
Oxidized phospholipids (oxPAPC) induce endothelial dysfunction and atherosclerosis. Here we show that oxPAPC a gene network regulating serine-glycine metabolism with the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) as causal regulator using integrative modeling Bayesian analysis in human aortic cells. The cluster is activated plaque material by atherogenic lipoproteins isolated from plasma of patients coronary artery disease (CAD). Single nucleotide...
Abstract Mitochondria are increasingly recognized as cellular hubs to orchestrate signaling pathways that regulate metabolism, redox homeostasis, and cell fate decisions. Recent research revealed a role of mitochondria also in innate immune signaling; however, the mechanisms how affect signal transduction poorly understood. Here, we show NF‐κB pathway activated by TNF employs platform for amplification shuttling nucleus. treatment induces recruitment HOIP, catalytic component linear...
Peroxynitrite (PN) is likely to be generated in vivo from nitric oxide and superoxide. We have previously shown that prostacyclin synthase, a heme‐thiolate enzyme essential for regulation of vascular tone, nitrated inactivated by submicromolar concentrations PN [Zou, M.‐H. & Ullrich, V. (1996) FEBS Lett. 382 , 101–104] we studied the effect heme proteins on PN‐mediated nitration phenolic compounds model systems [Mehl, M., Daiber, A. (1999) Nitric Oxide: Biol. Chem. 2 259–269]. In present...
Calcineurin (CaN) is a Ca 2+ ‐and calmodulin (CaM)‐dependent serine/threonine phosphatase containing dinuclear Fe–Zn center in the active site. Recent studies have indicated that CaN possible candidate for redox regulation. The inactivation of bovine brain and catalytic A‐subunit from Dictyostelium by vicinal dithiol reagents phenylarsine oxide (PAO) melarsen (MEL) H 2 O was investigated. PAO MEL inhibited with an IC 50 3–8 µ m reversed 2,3‐dimercapto‐1‐propane sulfonic acid. treatment...
Macrophages in the tumor microenvironment respond to complex cytokine signals. How these responses shape phenotype of tumor-associated macrophages (TAMs) is incompletely understood. Here we explored how cytokines milieu, interleukin (IL)-6 and IL-4, interact influence target gene expression primary human monocyte-derived (hMDMs). We show that dual stimulation with IL-4 IL-6 synergistically modified expression. Among induced genes are several targets known pro-tumorigenic properties, such as...
Macrophages exposed to the Th2 cytokines interleukin (IL) IL-4 and IL-13 exhibit a distinct transcriptional response, commonly referred as M2 polarization. Recently, IL-4-induced polarization of murine bone marrow-derived macrophages has been linked acetyl-CoA levels through activity cytosolic acetyl-CoA-generating enzyme ATP-citrate lyase (ACLY). Here, we studied how ACLY regulated IL-4-stimulated gene expression in human primary macrophages. Although multiple inhibitors attenuated target...
Macrophages respond to the Th2 cytokine IL-4 with elevated expression of arachidonate 15-lipoxygenase (ALOX15). Although signaling elicits anti-inflammatory responses, may either support or inhibit inflammatory processes in a context-dependent manner. AMP-activated protein kinase (AMPK) is metabolic sensor/regulator that supports an macrophage phenotype. How AMPK activation linked IL-4-elicited gene signatures remains unexplored. Using primary human macrophages stimulated IL-4, we observed...
Arachidonate 15-Lipoxygenase (ALOX15) and arachidonate 15-Lipoxygenase, Type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 and/or interleukin-13. Known primarily for roles bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated various macrophage functions including efferocytosis ferroptosis. Using a combination inhibitors siRNAs to...