Various avenues to counteract TNF – crucial to tackling acute inflammation

Claude Libert (VIB/UGent): “My research group has been working on TNF for many years, due to its important role in processes such as inflammation. For example, we discovered that inflammation develops almost exclusively after TNF binds to TNFR1. We have also seen that the concentration of this receptor determines the extent of the inflammation. Therefore, we recently developed an antibody that blocks TNFR1. Perhaps this can be used in the future to combat inflammation.” 

The aim of the VIB researchers is not only to block TNFR1, but they also want to gain a better understanding of how it is regulated. In other words, which mechanisms cause a decrease in TNFR1 expression. This could also be used in a therapeutic setting.

The group of Claude Libert discovered that a particular mouse strain, called SPRET/Ei, exhibits barely any response to TNF. Extensive research revealed that this is the result of very low expression of TNFR1 in these mice, which in turn is caused by the elevated expression of a micro-RNA molecule called miR-511.

Claude Libert: “Injection of this miR-511 did indeed cause a decrease in TNFR1 in these mice and made the mice resistant to TNF. Further research will have to be performed in the future to determine whether such miR injections can have a therapeutic use.

Glucocorticoids, steroids that are often prescribed to combat inflammation, were found to increase the expression of miR-511. Therefore, the effect of glucocorticoids is probably partly attributable to the fact that they cause a decrease in the concentration of TNFR1 via this molecular mechanism, resulting in a decreased response to TNF.

The fiendish behavior of TNF can be counteracted by microRNA, Cavaillon et al., EMBO Mol Med. 2015