Human astrocytes: secretome profiles of cytokines and chemokines

• Published in: PloS one 2014-04, Vol.9 (4), p.e92325
• Main Authors: Choi, Sung S, Lee, Hong J, Lim, Inja, Satoh, Jun-ichi, Kim, Seung U
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Astrocytes; Astrocytes - drug effects; Astrocytes - secretion; Bioinformatics; Biology and Life Sciences; Brain; Brain research; CCL3 protein; Cells, Cultured; Central nervous system; Cerebrospinal fluid; Chemokines; Chemokines - secretion; CXCL10 protein; Cytokines; DNA microarrays; Down-Regulation - drug effects; Fetuses; Gene expression; Genes; Genetic aspects; Glial Fibrillary Acidic Protein - metabolism; Granulocyte colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Growth factors; Humans; Inflammation; Interleukin 1 receptor antagonist; Interleukin 1 receptors; Interleukin 6; Interleukin 8; Interleukin-1beta - pharmacology; IP-10 protein; Lesions; Ligands; Medical research; Medicine; Medicine and Health Sciences; Monocyte chemoattractant protein 1; Multiple sclerosis; Nervous system; Neurological diseases; Neuronal-glial interactions; Neuroprotection; Neurotoxicity; NF-κB protein; Physiological aspects; Protein arrays; Proteins; Proteome - secretion; Research and Analysis Methods; Signal transduction; Signal Transduction - drug effects; Signaling; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Up-Regulation - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0092325

Astrocytes play a key role in maintenance of neuronal functions in the central nervous system by producing various cytokines, chemokines, and growth factors, which act as a molecular coordinator of neuron-glia communication. At the site of neuroinflammation, astrocyte-derived cytokines and chemokines play both neuroprotective and neurotoxic roles in brain lesions of human neurological diseases. At present, the comprehensive profile of human astrocyte-derived cytokines and chemokines during inflammation remains to be fully characterized. We investigated the cytokine secretome profile of highly purified human astrocytes by using a protein microarray. Non-stimulated human astrocytes in culture expressed eight cytokines, including G-CSF, GM-CSF, GROα (CXCL1), IL-6, IL-8 (CXCL8), MCP-1 (CCL2), MIF and Serpin E1. Following stimulation with IL-1β and TNF-α, activated astrocytes newly produced IL-1β, IL-1ra, TNF-α, IP-10 (CXCL10), MIP-1α (CCL3) and RANTES (CCL5), in addition to the induction of sICAM-1 and complement component 5. Database search indicated that most of cytokines and chemokines produced by non-stimulated and activated astrocytes are direct targets of the transcription factor NF-kB. These results indicated that cultured human astrocytes express a distinct set of NF-kB-target cytokines and chemokines in resting and activated conditions, suggesting that the NF-kB signaling pathway differentially regulates gene expression of cytokines and chemokines in human astrocytes under physiological and inflammatory conditions.