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Immunomodulation by interleukin-33 is protective in stroke through modulation of inflammation.
Korhonen, Paula; Kanninen, Katja M; Lehtonen, Sárka; Lemarchant, Sighild; Puttonen, Katja A; Oksanen, Minna; Dhungana, Hiramani; Loppi, Sanna; Pollari, Eveliina; Wojciechowski, Sara; Kidin, Iurii; García-Berrocoso, Teresa; Giralt, Dolors; Montaner, Joan; Koistinaho, Jari; Malm, Tarja.
Afiliación
  • Korhonen P; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Kanninen KM; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Lehtonen S; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Lemarchant S; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Puttonen KA; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Oksanen M; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Dhungana H; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Loppi S; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Pollari E; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Wojciechowski S; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • Kidin I; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
  • García-Berrocoso T; Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
  • Giralt D; Neurovascular Research Laboratory, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Pg. Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
  • Montaner J; Neurovascular Unit, Department of Neurology, Vall d'Hebron Hospital, Barcelona, Spain.
  • Koistinaho J; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland. Electronic address: jari.koistinaho@uef.fi.
  • Malm T; Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
Brain Behav Immun ; 49: 322-36, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26111431
Cerebral stroke induces massive Th1-shifted inflammation both in the brain and the periphery, contributing to the outcome of stroke. A Th1-type response is neurotoxic whereas a Th2-type response is accompanied by secretion of anti-inflammatory cytokines, such as interleukin-4 (IL-4). Interleukin-33 (IL-33) is a cytokine known to induce a shift towards the Th2-type immune response, polarize macrophages/microglia towards the M2-type, and induce production of anti-inflammatory cytokines. We found that the plasma levels of the inhibitory IL-33 receptor, sST2, are increased in human stroke and correlate with a worsened stroke outcome, suggesting an insufficient IL-33-driven Th2-type response. In mouse, peripheral administration of IL-33 reduced stroke-induced cell death and improved the sensitivity of the contralateral front paw at 5days post injury. The IL-33-treated mice had increased levels of IL-4 in the spleen and in the peri-ischemic area of the cortex. Neutralization of IL-4 by administration of an IL-4 antibody partially prevented the IL-33-mediated protection. IL-33 treatment also reduced astrocytic activation in the peri-ischemic area and increased the number of Arginase-1 immunopositive microglia/macrophages at the lesion site. In human T-cells, IL-33 treatment induced IL-4 secretion, and the conditioned media from IL-33-exposed T-cells reduced astrocytic activation. This study demonstrates that IL-33 is protective against ischemic insult by induction of IL-4 secretion and may represent a novel therapeutic approach for the treatment of stroke.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Receptores de Somatostatina / Accidente Cerebrovascular / Interleucina-33 / Inflamación Límite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Receptores de Somatostatina / Accidente Cerebrovascular / Interleucina-33 / Inflamación Límite: Aged / Animals / Female / Humans / Male Idioma: En Revista: Brain Behav Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Año: 2015 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Países Bajos