title: A role for human brain pericytes in neuroinflammation.
abstract: 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.
authors.forename: Deidre
authors.initials: D
authors.lastname: Jansson
authors.forename: Justin
authors.initials: J
authors.lastname: Rustenhoven
authors.forename: Sheryl
authors.initials: S
authors.lastname: Feng
authors.forename: Daniel
authors.initials: D
authors.lastname: Hurley
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Oldfield
authors.forename: Peter S
authors.initials: PS
authors.lastname: Bergin
authors.forename: Edward W
authors.initials: EW
authors.lastname: Mee
authors.forename: Richard L M
authors.initials: RL
authors.lastname: Faull
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 85 Park Road, Auckland 1023, New Zealand. m.dragunow@auckland.ac.nz.
authors.forename: Mike
authors.initials: M
authors.lastname: Dragunow
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism; D004827:Epilepsy / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000187:drug effects; D009924:Organ Culture Techniques; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000199:Actins; D000941:Antigens; D016207:Cytokines; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D017493:Leukocyte Common Antigens; D011509:Proteoglycans; D020797:Receptor, Platelet-Derived Growth Factor beta; D051996:Transcription Factor RelA; D000099216:Chondroitin Sulfate Proteoglycan 4; C541116:ACTA2 protein, human