title: Human astrocytes: secretome profiles of cytokines and chemokines.
abstract: 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.
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Sung S
authors.initials: SS
authors.lastname: Choi
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Hong J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Physiology, Chung-Ang University College of Medicine, Seoul, Korea.
authors.forename: Inja
authors.initials: I
authors.lastname: Lim
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Kiyose, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Satoh
authors.affiliation: Medical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea; Division of Neurology, Department of Medicine, UBC Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
mesh_terms: D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018925:Chemokines; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha