June 18, 2019
Introduction: Activation of brain immune cells (microglia) leads to the secretion by those activated microglia of chemicals that can injure or kill neurons. Microglial activation, which can also help neurons survive, is believed to mediate neuron death following both acute insults (such as stroke, gunshot wounds, etc) and chronic conditions (degenerative brain diseases, multiple sclerosis, etc). Drugs that inhibit microglial activation could serve as therapies for these conditions.
We have explored the possibility of using human microglia in cell culture as models for brain neuro-inflammation. This would allow rapid screening of drugs that might lower inflammation.
Results: We used SV-40 transformed human microglia (obtained from ATCC) as the cell model. We observed that all activators tested (lipopolysaccharide (LPS); transforming growth factor beta (TGFb); interleukin-4 (IL4), interferon-gamma (IFNg); and IL4+TGFb) caused increases in mRNA gene expression in the microglia (Figure 1). We used PBS/BSA solution as vehicle control.
To demonstrate potential utility of this cell model, we compared the expression of regulatory (epigenetic) microRNA (miRNA) genes in microglia compared to miRNA expression in hNSCP’s, both cell lines exposed to the toxin chlorpyrifos. We found an excellent correlation among the miRNA’s in both cell types (correlation r = 0.7, p < 0.0001). Figure 2 shows this correlation.
Interpretation: Our findings support the continued development of human microglial cells in culture as a model for neuro-inflammation. If confirmed, these cells could serve as a platform for rapid and efficient screening of drugs that inhibit neuro-inflammation and may have therapeutic actions.