Human Astrocytes: Secretome Profiles of Cytokines and Chemokines

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Apr 3

PMID 24691121

Citations 230

Authors

Sung S Choi

Hong J Lee

Inja Lim

Jun-Ichi Satoh

Seung U Kim

Affiliations

Soon will be listed here.

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.

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References

Sofroniew M, Vinters H . Astrocytes: biology and pathology. Acta Neuropathol. 2009; 119(1):7-35. PMC: 2799634. DOI: 10.1007/s00401-009-0619-8. View

Schabitz W, Kruger C, Pitzer C, Weber D, Laage R, Gassler N . A neuroprotective function for the hematopoietic protein granulocyte-macrophage colony stimulating factor (GM-CSF). J Cereb Blood Flow Metab. 2007; 28(1):29-43. DOI: 10.1038/sj.jcbfm.9600496. View

Barres B . The mystery and magic of glia: a perspective on their roles in health and disease. Neuron. 2008; 60(3):430-40. DOI: 10.1016/j.neuron.2008.10.013. View

Bajetto A, Bonavia R, Barbero S, Schettini G . Characterization of chemokines and their receptors in the central nervous system: physiopathological implications. J Neurochem. 2002; 82(6):1311-29. DOI: 10.1046/j.1471-4159.2002.01091.x. View

Takeshita Y, Ransohoff R . Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models. Immunol Rev. 2012; 248(1):228-39. PMC: 3383666. DOI: 10.1111/j.1600-065X.2012.01127.x. View

Hua L, Lee S . Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia. Glia. 2000; 30(1):74-81. DOI: 10.1002/(sici)1098-1136(200003)30:1<74::aid-glia8>3.0.co;2-c. View

Lee S, Liu W, Dickson D, Brosnan C, Berman J . Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol. 1993; 150(7):2659-67. View

Rothwarf D, Karin M . The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleus. Sci STKE. 2002; 1999(5):RE1. DOI: 10.1126/stke.1999.5.re1. View

Aloisi F, Care A, Borsellino G, Gallo P, Rosa S, Bassani A . Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha. J Immunol. 1992; 149(7):2358-66. View

10.

Meeuwsen S, Persoon-Deen C, Bsibsi M, Ravid R, van Noort J . Cytokine, chemokine and growth factor gene profiling of cultured human astrocytes after exposure to proinflammatory stimuli. Glia. 2003; 43(3):243-53. DOI: 10.1002/glia.10259. View

11.

Skalnikova H, Motlik J, Gadher S, Kovarova H . Mapping of the secretome of primary isolates of mammalian cells, stem cells and derived cell lines. Proteomics. 2011; 11(4):691-708. DOI: 10.1002/pmic.201000402. View

12.

Carney D, Haviland D, Noack D, Wetsel R, Vik D, Tack B . Structural aspects of the human C5 gene. Intron/exon organization, 5'-flanking region features, and characterization of two truncated cDNA clones. J Biol Chem. 1991; 266(28):18786-91. View

13.

Kim M, Suh H, Brosnan C, Lee S . Regulation of RANTES/CCL5 expression in human astrocytes by interleukin-1 and interferon-beta. J Neurochem. 2004; 90(2):297-308. DOI: 10.1111/j.1471-4159.2004.02487.x. View

14.

Simpson J, Newcombe J, Cuzner M, Woodroofe M . Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol. 1998; 84(2):238-49. DOI: 10.1016/s0165-5728(97)00208-7. View

15.

Satoh J . Molecular network of ChIP-Seq-based NF-κB p65 target genes involves diverse immune functions relevant to the immunopathogenesis of multiple sclerosis. Mult Scler Relat Disord. 2015; 3(1):94-106. DOI: 10.1016/j.msard.2013.04.005. View

16.

Chen L, Yang G, Zhang X, Wu J, Gu Q, Wei M . Induction of MIF expression by oxidized LDL via activation of NF-kappaB in vascular smooth muscle cells. Atherosclerosis. 2009; 207(2):428-33. DOI: 10.1016/j.atherosclerosis.2009.05.021. View

17.

Barnes P, Karin M . Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997; 336(15):1066-71. DOI: 10.1056/NEJM199704103361506. View

18.

Gilmore T . Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006; 25(51):6680-4. DOI: 10.1038/sj.onc.1209954. View

19.

Xia M, Bacskai B, Knowles R, Qin S, Hyman B . Expression of the chemokine receptor CXCR3 on neurons and the elevated expression of its ligand IP-10 in reactive astrocytes: in vitro ERK1/2 activation and role in Alzheimer's disease. J Neuroimmunol. 2000; 108(1-2):227-35. DOI: 10.1016/s0165-5728(00)00285-x. View

20.

Tokami H, Ago T, Sugimori H, Kuroda J, Awano H, Suzuki K . RANTES has a potential to play a neuroprotective role in an autocrine/paracrine manner after ischemic stroke. Brain Res. 2013; 1517:122-32. DOI: 10.1016/j.brainres.2013.04.022. View