title: Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization.
abstract: Macrophage polarization elicits various metabolic alterations which in turn influence the polarized phenotype. Activation of glycolytic metabolism accompanies and supports macrophage pro-inflammatory M1 polarization. In contrast, M2 polarization of murine macrophages in response to the Th2 cytokine interleukin-4 (IL-4) was linked to the up-regulation of mitochondrial oxidative metabolism and fatty acid oxidation (FAO), which was necessary for coining an IL-4-polarized phenotype. Here we investigated whether similar mechanisms operate in human macrophages stimulated with IL-4. IL-4 causes only moderate changes of mitochondrial oxidative metabolism and FAO, correlating with an unaltered expression of peroxisome proliferator-activated receptor-γ coactivator 1 α/β (PGC-1α/β), the master transcriptional regulators of mitochondrial biogenesis. Furthermore, attenuating FAO had no effect on IL-4-induced polarization-associated gene expression. Apparently, FAO is dispensable for IL-4-induced polarization of human macrophages, pointing to fundamental differences in the metabolic requirements of macrophage phenotype alterations between mice and humans.
authors: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I/ZAFES, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
authors: Dmitry
authors: D
authors: Namgaladze
authors: Goethe-University Frankfurt, Faculty of Medicine, Institute of Biochemistry I/ZAFES, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Electronic address: bruene@pathobiochemie1.de.
authors: Bernhard
authors: B
authors: Brüne
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000819:agonists / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000145:classification / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D005227:Fatty Acids; C508598:IL4 protein, human; C486497:PPARGC1A protein, human; C455622:PPARGC1B protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D015847:Interleukin-4
keywords: Beta‐oxidation; Interleukin; Macrophages; Mitochondrial metabolism; Transcription coactivators