A role for human brain pericytes in neuroinflammation

Journal of Neuroinflammation

Mike Dragunow⁴  Richard LM Faull⁴  Edward W Mee²  Peter S Bergin²  Robyn L Oldfield³  Daniel Hurley¹  Sheryl Feng⁴  Justin Rustenhoven⁴  Deidre Jansson⁴ 

[1] Department of Molecular Medicine and Pathology, The University of Auckland, Bldg 504, 85 Park Road, Auckland 1023, New Zealand;Auckland City Hospital, 2 Park Rd, Auckland 1010, New Zealand;LabPLUS, Auckland City Hospital, Bldg 31, Gate 4 Grafton Road, Auckland 1148, New Zealand;Centre for Brain Research, The University of Auckland, Bldg 503, 85 Park Road, Auckland 1023, New Zealand

关键词: Chemokines;    Blood–brain barrier;    Inflammation;    Astrocytes;    Microglia;   

Others  :  1151602
DOI  :  10.1186/1742-2094-11-104

 received in 2013-12-18, accepted in 2014-05-19,  发布年份 2014

【 摘 要 】

Background

Brain inflammation plays a key role in neurological disease. Although much research has been conducted investigating inflammatory events in animal models, potential differences in human brain versus rodent models makes it imperative that we also study these phenomena in human cells and tissue.

Methods

Primary human brain cell cultures were generated from biopsy tissue of patients undergoing surgery for drug-resistant epilepsy. Cells were treated with pro-inflammatory compounds IFNγ, TNFα, IL-1β, and LPS, and chemokines IP-10 and MCP-1 were measured by immunocytochemistry, western blot, and qRT-PCR. Microarray analysis was also performed on late passage cultures treated with vehicle or IFNγ and IL-1β.

Results

Early passage human brain cell cultures were a mixture of microglia, astrocytes, fibroblasts and pericytes. Later passage cultures contained proliferating fibroblasts and pericytes only. Under basal culture conditions all cell types showed cytoplasmic NFκB indicating that they were in a non-activated state. Expression of IP-10 and MCP-1 were significantly increased in response to pro-inflammatory stimuli. The two chemokines were expressed in mixed cultures as well as cultures of fibroblasts and pericytes only. The expression of IP-10 and MCP-1 were regulated at the mRNA and protein level, and both were secreted into cell culture media. NFκB nuclear translocation was also detected in response to pro-inflammatory cues (except IFNγ) in all cell types. Microarray analysis of brain pericytes also revealed widespread changes in gene expression in response to the combination of IFNγ and IL-1β treatment including interleukins, chemokines, cellular adhesion molecules and much more.

Conclusions

Adult human brain cells are sensitive to cytokine challenge. As expected ‘classical’ brain immune cells, such as microglia and astrocytes, responded to cytokine challenge but of even more interest, brain pericytes also responded to such challenge with a rich repertoire of gene expression. Immune activation of brain pericytes may play an important role in communicating inflammatory signals to and within the brain interior and may also be involved in blood brain barrier (BBB) disruption . Targeting brain pericytes, as well as microglia and astrocytes, may provide novel opportunities for reducing brain inflammation and maintaining BBB function and brain homeostasis in human brain disease.

【 授权许可】

   
2014 Jansson et al.; licensee BioMed Central Ltd.

【 图 表 】

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