Human astrocytes: secretome profiles of cytokines and chemokines

PLoS One. 2014 Apr 1;9(4):e92325. doi: 10.1371/journal.pone.0092325. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Chemokines / metabolism*
  • Down-Regulation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Interleukin-1beta / pharmacology
  • Proteome / metabolism*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology
  • Up-Regulation / drug effects

Substances

  • Chemokines
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • Proteome
  • Tumor Necrosis Factor-alpha

Grants and funding

The present study was supported by the Korea Healthcare Technology R&D Project HI12C0167 (A120214) and Canadian Myelin Research Initiative. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.