title: Microglial HO-1 induction by curcumin provides antioxidant, antineuroinflammatory, and glioprotective effects.
abstract: METHODS
  We have studied if curcumin can protect glial cells under an oxidative stress and inflammatory environment, which is known to be deleterious in neurodegeneration.
  
  
  RESULTS
  Primary rat glial cultures exposed to the combination of an oxidative (rotenone/oligomycin A) and a proinflammatory LPS stimuli reduced by 50% glial viability. Under these experimental conditions, curcumin afforded significant glial protection and reduction of reactive oxygen species; these effects were blocked by the HO-1 inhibitor tin protoporphyrin-IX (SnPP). These findings correlate with the observation that curcumin induced the antioxidative protein HO-1. Most interesting was the observation that the glial protective effects related to HO-1 induction were microglial specific as shown in glial cultures from LysM(Cre) Hmox(∆/∆) mice where curcumin lost its protective effect. Under LPS conditions, curcumin reduced the microglial proinflammatory markers iNOS and tumor necrosis factor, but increased the anti-inflammatory cytokine IL4. Analysis of the microglial phenotype showed that curcumin favored a ramified morphology toward a microglial alternative activated state against LPS insult also by a HO-1-dependent mechanism.
  
  
  CONCLUSIONS
  The curry constituent curcumin protects glial cells and promotes a microglial anti-inflammatory phenotype by a mechanism that implicates HO-1 induction; these effects may have impact on brain protection under oxidative and inflammatory conditions.
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Parada
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Buendia
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Navarro
authors.affiliation: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Avendaño
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Egea
authors.affiliation: Instituto Teófilo Hernando, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.|Instituto de Investigación Sanitaria Princesa (IIS-IP), Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008665:Metalloporphyrins / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011524:Protoporphyrins / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; C032628:tin protoporphyrin IX; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D003474:Curcumin
keywords: Curcumin; Hemoxygenase-1; Inflammation; Microglia; Oxidative stress