PMID- 16554469 OWN - NLM STAT- MEDLINE DCOM- 20060414 LR - 20191008 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 26 IP - 12 DP - 2006 Mar 22 TI - Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. PG - 3182-91 AB - Many studies have shown that transplanted or endogenous neural progenitor cells will migrate toward damaged areas of the brain. However, the mechanism underlying this effect is not clear. Here we report that, using hippocampal slice cultures, grafted neural progenitor cells (NPs) migrate toward areas of neuroinflammation and that chemokines are a major regulator of this process. Migration of NPs was observed after injecting an inflammatory stimulus into the area of the fimbria and transplanting enhanced green fluorescent protein (EGFP)-labeled NPs into the dentate gyrus of cultured hippocampal slices. Three to 7 d after transplantation, EGFP-NPs in control slices showed little tendency to migrate and had differentiated into neurons and glia. In contrast, in slices injected with inflammatory stimuli, EGFP-NPs migrated toward the site of the injection. NPs in these slices also survived less well. The inflammatory stimuli used were a combination of the cytokines tumor necrosis factor-alpha and interferon-gamma, the bacterial toxin lipopolysaccharide, the human immunodeficiency virus-1 coat protein glycoprotein 120, or a beta-amyloid-expressing adenovirus. We showed that these inflammatory stimuli increased the synthesis of numerous chemokines and cytokines by hippocampal slices. When EGFP-NPs from CC chemokine receptor CCR2 knock-out mice were transplanted into slices, they exhibited little migration toward sites of inflammation. Similarly, wild-type EGFP-NPs exhibited little migration toward inflammatory sites when transplanted into slices prepared from monocyte chemoattractant protein-1 (MCP-1) knock-out mice. These data indicate that factors secreted by sites of neuroinflammation are attractive to neural progenitors and suggest that chemokines such as MCP-1 play an important role in this process. FAU - Belmadani, Abdelhak AU - Belmadani A AD - Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA. FAU - Tran, Phuong B AU - Tran PB FAU - Ren, Dongjun AU - Ren D FAU - Miller, Richard J AU - Miller RJ LA - eng GR - R01 DA013141/DA/NIDA NIH HHS/United States GR - R01 DA013141-04/DA/NIDA NIH HHS/United States GR - R37MH040165/MH/NIMH NIH HHS/United States GR - R01DA013141/DA/NIDA NIH HHS/United States GR - R01NS043095/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (CCR2 protein, human) RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Brain Tissue Transplantation/methods MH - Cell Differentiation/physiology MH - Cell Movement/*physiology MH - Cells, Cultured MH - Chemokine CCL2/genetics MH - Chemokines/immunology/*metabolism MH - Cytokines/immunology/metabolism MH - Encephalitis/immunology/*metabolism/physiopathology MH - Graft Survival/physiology MH - Green Fluorescent Proteins MH - Hippocampus/cytology/immunology/metabolism MH - Inflammation Mediators/pharmacology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Inbred ICR MH - Mice, Knockout MH - Mice, Transgenic MH - Neurons/immunology/*metabolism MH - Organ Culture Techniques MH - Receptors, CCR2 MH - Receptors, Chemokine/genetics MH - Stem Cell Transplantation/methods MH - Stem Cells/immunology/*metabolism PMC - PMC2740990 MID - NIHMS103228 EDAT- 2006/03/24 09:00 MHDA- 2006/04/15 09:00 PMCR- 2006/09/22 CRDT- 2006/03/24 09:00 PHST- 2006/03/24 09:00 [pubmed] PHST- 2006/04/15 09:00 [medline] PHST- 2006/03/24 09:00 [entrez] PHST- 2006/09/22 00:00 [pmc-release] AID - 26/12/3182 [pii] AID - 10.1523/JNEUROSCI.0156-06.2006 [doi] PST - ppublish SO - J Neurosci. 2006 Mar 22;26(12):3182-91. doi: 10.1523/JNEUROSCI.0156-06.2006.