title: Anti-inflammatory role of Leptin in glial cells through p38 MAPK pathway inhibition.
abstract: BACKGROUND
  In the present work, we studied the modulatory effect of Leptin (Lep) against pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFα), interleukin 1-beta (IL1β) and interferon-gamma (IFNγ), in primary glial cell cultures.
  
  
  METHODS
  Glial cultures were treated with pro-inflammatory cytokines (TNFα, 20ng/ml; IL1β, 20ng/ml; IFNγ 20ng/ml). Cells were pre-treated with Lep 500nM, 1h prior to cytokine treatment. NO released from glial cells was determined using the Griess reaction. Cell viability was determined by the MTT method. Protein expression was determined by western blot.
  
  
  RESULTS
  Pre-treatment with 500nM Lep produced an inhibitory effect on inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production after glial cells exposure to pro-inflammatory cytokines. Anti-inflammatory effect can be related to a decrease in P38 MAP Kinase (MAPK) pathway activity. Treatment of glial cell cultures with Lep also reduced the intrinsic apoptotic pathway (cytochrome c release and caspase-3 activation).
  
  
  CONCLUSIONS
  We suggest that Lep would act as an anti-inflammatory factor in glial cells exposed to pro-inflammatory cytokines, exerting its function on p38 MAPK pathway and reducing NO production.
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Patraca
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Nohora
authors.initials: N
authors.lastname: Martínez
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Busquets
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Martí
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain; Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pedrós
authors.affiliation: Departamento de Biología Celular y Molecular, C.U.C.B.A., Universidad de Guadalajara, División de Neurociencias, Guadalajara, Jalisco, Mexico; Instituto Mexicano del Seguro Social (IMSS), Centro de Investigación Biomédica de Occidente (CIBO), Guadalajara, Jalisco, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Beas-Zarate
authors.affiliation: Centro de Biotecnología, Universidad Nacional de Loja, La Argelia, Loja, Ecuador.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marin
authors.affiliation: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Ettcheto
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Sureda
authors.affiliation: Departament de Biologia Cel·lular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Auladell
authors.affiliation: Unitat de Farmacologia i Farmacognòsia, Institut de Neurociencias, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain; Centro de Biotecnología, Universidad Nacional de Loja, La Argelia, Loja, Ecuador. Electronic address: camins@ub.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.affiliation: Unitats de Bioquímica i Farmacologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, (Tarragona), Spain; Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Folch
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007371:Interferon-gamma / Q000008:administration & dosage / Q000378:metabolism; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D053583:Interleukin-1beta; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Caspase-3; Cytochrome-c; Glial cells; Leptin; iNOS; p38 MAPK