脳内細胞間情報伝達物質としてのサイトカイン・ケモカイン

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The brain includes glial cells (astrocytes, microglia and oligodendrocytes) and endothelial cells in addition to neurons. Under some pathological conditions, it is invaded by leukocytes such as neutrophils, monocytes/macrophages and lymphocytes. Intercellular communication across these cell species is supposed to play crucial roles both in the brain functions and dysfunctions. However, the molecular basis of such intercellular communication remains unclear. We have studied the roles of cytokines and chemokines, which have been investigated as essential mediators in the immune and inflammatory systems, in intercellular communication across neurons, glial cells, endothelial cells and leukocytes. Messenger RNA expression of cytokines such as interleukin-1β was induced in brain microglia by i.p. injection of excitotoxin and neurostimulant, at least, partly via catecholaminergic systems. Messenger RNA of other cytokines such as leukemia inhibitory factor was induced in astrocytes. This cytokine specifically induced nociceptin mRNA in the cultured cortical neurons. Constitutive expression of some chemokines such as fractalkine and stromal cell derivd factor-1α was observed in the brain, suggesting that they play improtant roles in maintenance of brain homeostasis or determination of the patterning of neurons and/or glial cells in the devloping and adult brains. Cytokines such as interleukin-1β and chemokines such as monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α were produced in ischemic brain and implicated in ischemic brain injury. In addition to ischemia, cytokines, chemokines and their receptors have been shown to be involved in various neurodegenerative diseases such as multiple sclerosis, Alzheimer's disease and AIDS dementia syndrome. They are potential targets for therapeutic intervention for neurodegenerative diseases.
公益社団法人日本薬学会の論文
2001-12-01

脳内細胞間情報伝達物質としてのサイトカイン・ケモカイン

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