title: Pivotal Advance: Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes.
abstract: In macrophages, basal polyamine (putrescine, spermidine, and spermine) levels are relatively low but are increased upon IL-4 stimulation. This Th2 cytokine induces Arg1 activity, which converts arginine into ornithine, and ornithine can be decarboxylated by ODC to produce putrescine, which is further converted into spermidine and spermine. Recently, we proposed polyamines as novel agents in IL-4-dependent E-cadherin regulation in AAMs. Here, we demonstrate for the first time that several, but not all, AAM markers depend on polyamines for their IL-4-induced gene and protein expression and that polyamine dependency of genes relies on the macrophage type. Remarkably, Arg1-deficient macrophages display rather enhanced IL-4-induced polyamine production, suggesting that an Arg1-independent polyamine synthesis pathway may operate in macrophages. On the other side of the macrophage activation spectrum, LPS-induced expression of several proinflammatory genes was increased significantly in polyamine-depleted CAMs. Overall, we propose Arg1 independently produced polyamines as novel regulators of the inflammatory status of the macrophage. Indeed, whereas polyamines are needed for IL-4-induced expression of several AAM mediators, they inhibit the LPS-mediated expression of proinflammatory genes in CAMs.
authors.affiliation: Myeloid Cell Immunology Lab, VIB-Vrije Universiteit Brussel, Building E, Level 8, Pleinlaan 2, B-1050, Brussels, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van den Bossche
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.forename: Eleonore S
authors.initials: ES
authors.lastname: Koehler
authors.forename: Jan M C
authors.initials: JM
authors.lastname: Geuns
authors.forename: Leena
authors.initials: L
authors.lastname: Alhonen
authors.forename: Anne
authors.initials: A
authors.lastname: Uimari
authors.forename: Sini
authors.initials: S
authors.lastname: Pirnes-Karhu
authors.forename: Eva
authors.initials: E
authors.lastname: Van Overmeire
authors.forename: Yannick
authors.initials: Y
authors.lastname: Morias
authors.forename: Lea
authors.initials: L
authors.lastname: Brys
authors.forename: Lars
authors.initials: L
authors.lastname: Vereecke
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
mesh_terms: D000818:Animals; D001119:Arginase / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011073:Polyamines / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D042787:Receptor, TIE-2
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011073:Polyamines; D012333:RNA, Messenger; D015847:Interleukin-4; D009569:Nitric Oxide; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase