Pro-inflammatory TNFα and IL-1β differentially regulate the inflammatory phenotype of brain microvascular endothelial cells

Journal of Neuroinflammation

E. Scott Graham³  Catherine E. Angel²  Rebecca Johnson³  Odunayo Rotimi¹  Vicky Nelson³  Rachael Wiltshire⁴  Dan Ting Kho³  Simon J. O’Carroll¹ 

[1] Department of Anatomy, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;School of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand;Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;Centre for Brain Research, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

关键词: ECIS;    Human;    TNFα;    IL-1β;    Cytokine;    CBA;    Endothelial cells;    xCELLigence;   

Others  :  1221914
DOI  :  10.1186/s12974-015-0346-0

 received in 2014-12-21, accepted in 2015-06-17,  发布年份 2015

【 摘 要 】

Background

The vasculature of the brain is composed of endothelial cells, pericytes and astrocytic processes. The endothelial cells are the critical interface between the blood and the CNS parenchyma and are a critical component of the blood-brain barrier (BBB). These cells are innately programmed to respond to a myriad of inflammatory cytokines or other danger signals. IL-1β and TNFα are well recognised pro-inflammatory mediators, and here, we provide compelling evidence that they regulate the function and immune response profile of human cerebral microvascular endothelial cells (hCMVECs) differentially.

Methods

We used xCELLigence biosensor technology, which revealed global differences in the endothelial response between IL-1β and TNFα. xCELLigence is a label-free impedance-based biosensor, which is ideal for acute or long-term comparison of drug effects on cell behaviour. In addition, flow cytometry and multiplex cytokine arrays were used to show differences in the inflammatory responses from the endothelial cells.

Results

Extensive cytokine-secretion profiling and cell-surface immune phenotyping confirmed that the immune response of the hCMVEC to IL-1β was different to that of TNFα. Interestingly, of the 38 cytokines, chemokines and growth factors measured by cytometric bead array, the endothelial cells secreted only 13. Of importance was the observation that the majority of these cytokines were differentially regulated by either IL-1β or TNFα. Cell-surface expression of ICAM-1 and VCAM-1 were also differentially regulated by IL-1β or TNFα, where TNFα induced a substantially higher level of expression of both key leukocyte-adhesion molecules. A range of other cell-surface cellular and junctional adhesion molecules were basally expressed by the hCMVEC but were unaffected by IL-1β or TNFα.

Conclusions

To our knowledge, this is the most comprehensive analysis of the immunological profile of brain endothelial cells and the first direct evidence that human brain endothelial cells are differentially regulated by these two key pro-inflammatory mediators.

【 授权许可】

   
2015 O’Carroll et al.

【 图 表 】

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