title: Suppression of dendritic cell functions contributes to the anti-inflammatory action of granulocyte-colony stimulating factor in experimental stroke.
abstract: Cerebral ischemia provokes an inflammatory cascade, which is assumed to secondarily worsen ischemic tissue damage. Linking adaptive and innate immunity dendritic cells (DCs) are key regulators of the immune system. The hematopoietic factor G-CSF is able to modulate DC-mediated immune processes. Although G-CSF is under investigation for the treatment of stroke, only limited information exists about its effects on stroke-induced inflammation. Therefore, we investigated the impact of G-CSF on cerebral DC migration and maturation as well as on the mediated immune response in an experimental stroke model in rats by means of transient middle cerebral artery occlusion (tMCAO). Immunohistochemistry and quantitative PCR were performed of the ischemic brain and flow cytometrical analysis of peripheral blood. G-CSF led to a reduction of the infarct size and an improved neurological outcome. Immunohistochemistry confirmed a reduced migration of DCs and mature antigen-presenting cells after G-CSF treatment. Compared to the untreated tMCAO group, G-CSF led to an inhibited DC activation and maturation. This was shown by a significantly decreased cerebral transcription of TLR2 and the DC maturation markers, CD83 and CD86, as well as by an inhibition of stroke-induced increase in immunocompetent DCs (OX62⁺OX6⁺) in peripheral blood. Cerebral expression of the proinflammatory cytokine TNF-α was reduced, indicating an attenuation of cerebral inflammation. Our data suggest an induction of DC migration and maturation under ischemic conditions and identify DCs as a potential target to modulate postischemic cerebral inflammation. Suppression of both enhanced DC migration and maturation might contribute to the neuroprotective action of G-CSF in experimental stroke.
authors: Department of Neurology, University Hospital Erlangen, Erlangen, Germany.
authors: Barbara
authors: B
authors: Dietel
authors: Iwona
authors: I
authors: Cicha
authors: Bernd
authors: B
authors: Kallmünzer
authors: Miyuki
authors: M
authors: Tauchi
authors: Atilla
authors: A
authors: Yilmaz
authors: Werner G
authors: WG
authors: Daniel
authors: Stefan
authors: S
authors: Schwab
authors: Christoph D
authors: CD
authors: Garlichs
authors: Rainer
authors: R
authors: Kollmar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020521:Stroke / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor