PMID- 15194436
OWN - NLM
STAT- MEDLINE
DCOM- 20040812
LR  - 20131121
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 297
IP  - 1
DP  - 2004 Jul 1
TI  - Monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 are 
      involved in both excitotoxin-induced neurodegeneration and regeneration.
PG  - 197-211
AB  - Intrahippocamal injections of kainic acid (KA) significantly increase the 
      expression of monocyte chemoattractant protein-1 (MCP-1) and macrophage 
      inflammatory protein-2 (MIP-2) in the ipsilateral hippocampus at 2-4 h and 21-45 
      days post-administration, suggesting the possible involvement of these chemokines 
      in both neurodegenerative and regenerative processes. To examine the possible 
      role of these chemokines on neuronal cell death, hippocampal neurons were 
      incubated with either MCP-1 or MIP-2 in vitro and examined to assess the effects 
      on neuronal cell viability. These treatments resulted in significant neuronal 
      apoptosis that could be abrogated by prior treatment with the caspase-1 
      inhibitor, Z-VAD-FMK, the caspase-3 inhibitor, Z-DEVD-FMK, the Galphai inhibitor, 
      pertussis toxin, or the MAO-B inhibitor, (-)deprenyl. Furthermore, this chemokine 
      apoptotic effect could also be observed in vivo as intrahippocampal injections of 
      MCP-1 or MIP-2 resulted in the apoptosis of hippocampal neurons, thus supporting 
      a direct role of these chemokines in neuronal death. In contrast, 
      immunohistological analysis of kainic acid lesions on days 21-45 revealed 
      significant expression of MCP-1 and MIP-2 associated with reactive astrocytes and 
      macrophages, respectively, with no apoptotic populations being observed. These 
      results suggested that these chemokines might also mediate distinct biological 
      effects on local microenvironmental cell populations at various stages post 
      truama and during cellular repair. To address this possibility, astrocyte were 
      cultured in the presence or absence of these chemokines and examined by 
      microarray analysis for effects on astrocytes gene expression. A number of genes 
      encoding proteins associated with inflammation, cellular signaling, 
      differentiation, and repair were directly modulated by chemokine treatment. More 
      specifically, the RNA and protein expression of the neurotrophic factor, basic 
      fibroblast growth factor (bFGF), was found to be significantly increased upon 
      culture with MCP-1 and MIP-2. Conditioned media derived from chemokine-stimulated 
      astrocytes also facilitated bFGF-dependent neuronal cell differentiation and 
      promoted survival of H19-7 neurons in vitro, suggesting a possible role for 
      chemokine-activated astrocytes as a source of trophic support. Taken together, 
      these data support possible autocrine and paracrine roles for MCP-1 and MIP-2 in 
      both the "death and life" of hippocampal neurons following CNS injury.
FAU - Kalehua, A N
AU  - Kalehua AN
AD  - Laboratory of Immunology, Clinical Immunology Section, Molecular Neurobiology 
      Section, NIA/NIH, Baltimore, MD 21224, USA.
FAU - Nagel, J E
AU  - Nagel JE
FAU - Whelchel, L M
AU  - Whelchel LM
FAU - Gides, J J
AU  - Gides JJ
FAU - Pyle, R S
AU  - Pyle RS
FAU - Smith, R J
AU  - Smith RJ
FAU - Kusiak, J W
AU  - Kusiak JW
FAU - Taub, D D
AU  - Taub DD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Monokines)
RN  - 0 (Neurotoxins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Astrocytes/drug effects/immunology/metabolism
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects/physiology
MH  - Chemokine CCL2/*metabolism/pharmacology
MH  - Chemokine CXCL2
MH  - Culture Media, Conditioned/pharmacology
MH  - Disease Models, Animal
MH  - Encephalitis/immunology/*metabolism/physiopathology
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblast Growth Factor 2/genetics/metabolism
MH  - Hippocampus/immunology/metabolism/physiopathology
MH  - Kainic Acid
MH  - Macrophages/drug effects/immunology/metabolism
MH  - Male
MH  - Monokines/*metabolism/pharmacology
MH  - Nerve Degeneration/chemically induced/immunology/*metabolism
MH  - Nerve Regeneration/drug effects/*physiology
MH  - Neurodegenerative Diseases/immunology/*metabolism/physiopathology
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neurotoxins
MH  - Rats
MH  - Rats, Inbred F344
MH  - Up-Regulation/drug effects/physiology
EDAT- 2004/06/15 05:00
MHDA- 2004/08/13 05:00
CRDT- 2004/06/15 05:00
PHST- 2003/11/21 00:00 [received]
PHST- 2004/01/29 00:00 [revised]
PHST- 2004/06/15 05:00 [pubmed]
PHST- 2004/08/13 05:00 [medline]
PHST- 2004/06/15 05:00 [entrez]
AID - S0014482704001417 [pii]
AID - 10.1016/j.yexcr.2004.02.031 [doi]
PST - ppublish
SO  - Exp Cell Res. 2004 Jul 1;297(1):197-211. doi: 10.1016/j.yexcr.2004.02.031.