Intrathecal upregulation of granulocyte colony stimulating factor and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis.
To investigate cytokine/chemokine changes in amyotrophic lateral sclerosis (ALS), we simultaneously measured 16 cytokine/chemokines (interleukin [IL]-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 [p70], IL-13, IL-17, interferon-gamma, tumor necrosis factor-alpha, granulocyte colony stimulating factor [G-CSF], macrophage chemoattractant protein-1 [MCP-1], and macrophage inflammatory protein-1beta) in cerebrospinal fluid (CSF) and sera from 37 patients with sporadic ALS and 33 controls using a multiplexed fluorescent bead-based immunoassay. We also conducted immunohistochemical analyses from 8 autopsied ALS cases and 6 nonneurologic disease controls as well as cell culture analyses of relevant cytokines and their receptors. We found that concentrations of G-CSF and MCP-1 were significantly increased in ALS CSF compared with controls. In spinal cords, G-CSF was expressed in reactive astrocytes in ALS cases but not controls, whereas G-CSF receptor expression was significantly decreased in motor neurons of spinal cords from ALS cases. Biologically, G-CSF had a protective effect on the NSC34 cell line under conditions of both oxidative and nutritional stress. We suggested that G-CSF has potentially neuroprotective effects on motor neurons in ALS and that downregulation of its receptor might contribute to ALS pathogenesis. On the other hand, MCP-1 correlated with disease severity, which may aggravate motor neuron damage.
Tanaka
Masahito
M
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Kikuchi
Hitoshi
H
Ishizu
Takaaki
T
Minohara
Motozumi
M
Osoegawa
Manabu
M
Motomura
Kyoko
K
Tateishi
Takahisa
T
Ohyagi
Yasumasa
Y
Kira
Jun-ichi
J
D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000503:physiopathology; D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid; D018925:Chemokines / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000134:cerebrospinal fluid; D019610:Cytoprotection / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000134:cerebrospinal fluid* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid / Q000276:immunology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000134:cerebrospinal fluid* / Q000276:immunology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D018696:Neuroprotective Agents; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor