title: VIP impairs acquisition of the macrophage proinflammatory polarization profile.
abstract: This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti-inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MØ), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MØ) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MØ exposed to VIP exhibited an up-regulation of M-MØ gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MØ, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases.
authors.affiliation: Faculty of Biology, Department of Cell Biology, Complutense University, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Carrión
authors.affiliation: Faculty of Biology, Department of Cell Biology, Complutense University, Madrid, Spain.
authors.forename: Selene
authors.initials: S
authors.lastname: Pérez-García
authors.affiliation: Faculty of Medicine, Department of Cell Biology, Complutense University, Madrid, Spain; and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Faculty of Biology, Department of Cell Biology, Complutense University, Madrid, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Juarranz
authors.affiliation: Immuno-metabolism Laboratory, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Estrada-Capetillo
authors.affiliation: Immuno-metabolism Laboratory, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Amaya
authors.initials: A
authors.lastname: Puig-Kröger
authors.affiliation: Faculty of Biology, Department of Cell Biology, Complutense University, Madrid, Spain; gomariz@bio.ucm.es.
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
authors.affiliation: Faculty of Biology, Department of Cell Biology, Complutense University, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Cañas
mesh_terms: D001172:Arthritis, Rheumatoid / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013582:Synovial Fluid / Q000166:cytology; D015854:Up-Regulation; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000242:Cyclic AMP
keywords: anti-inflammatory; granulocyte; human monocyte; inflammation; rheumatoid arthritis