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F1000Res. 2016 Mar 03;5:270. doi: 10.12688/f1000research.8153.2. eCollection 2016.

IL-6 stimulates a concentration-dependent increase in MCP-1 in immortalised human brain endothelial cells.

F1000Research

Jai Min Choi, Odunayo O Rotimi, Simon J O'Carroll, Louise F B Nicholson

Affiliations

  1. Department of Anatomy and Medical Imaging and the Centre for Brain Research, Faculty of Medical and Health Sciences (FMHS), University of Auckland, Auckland, New Zealand.

PMID: 27347374 PMCID: PMC4900293 DOI: 10.12688/f1000research.8153.2

Abstract

Systemic inflammation is associated with neurodegeneration, with elevated interleukin-6 (IL-6) in particular being correlated with an increased risk of dementia. The brain endothelial cells of the blood brain barrier (BBB) serve as the interface between the systemic circulation and the brain microenvironment and are therefore likely to be a key player in the development of neuropathology associated with systemic inflammation. Endothelial cells are known to require soluble IL-6 receptor (sIL-6R) in order to respond to IL-6, but studies in rat models have shown that this is not the case for brain endothelial cells and studies conducted in human cells are limited. Here we report for the first time that the human cerebral microvascular cell line, hCMVEC, uses the classical mIL-6R signalling pathway in response to IL-6 in a concentration-dependent manner as measured by the production of monocyte chemotactic protein (MCP-1). This novel finding highlights a unique characteristic of human brain endothelial cells and that further investigation into the phenotype of this cell type is needed to elucidate the mechanisms of BBB pathology in inflammatory conditions.

Keywords: IL-6 stimulation; MCP-1; cell phenotype; systemic inflammation

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