Talia Kierstead, Wilfrid Laurier University

Kierstead, T¹., Sinopoli, S²., Gregory, D.E²., DeWitte-Orr, S.J¹. ¹Department of Health Sciences, Faculty of Science, Wilfrid Laurier University, Waterloo, ON, CA, ²Department of Kinesiology and Physical Education, Faculty of Science, Wilfrid Laurier University, Waterloo, ON, CA.

Fighting & Responding

Long double stranded RNA (LdsRNA) is a product of viral replication and a potent activator of the innate immune system. In mammals, LdsRNA typically induces type I interferon signalling but has been recently demonstrated to induce RNA interference (RNAi) at low concentrations. RNAi is a process that selectively silences complementary messenger RNAs (mRNAs). While RNAi has been primarily studied in the context of viral infection, its ability to control inflammation in non-viral contexts is worthy of investigation. The present study will examine whether LdsRNA can reduce inflammatory responses in annulus fibrosus (AF) cells, the resident cells of the intervertebral disc. These cells play a central role in the inflammation associated with low back pain. AF cells are treated with low doses of sequence specific dsRNA targeting pro-inflammatory mediators (MCP-1 and MIP-2) or a non-specific control (mCherry) to activate RNAi. To date, AF cells treated with MCP-1 LdsRNA demonstrated reduced MCP-1 product protein compared to mCherry LdsRNA controls, with MIP-2 LdsRNA's effect on MIP-2 protein expression currently under investigation. The role of LdsRNA in modifying AF cell wound healing is also being studied. This study examines the capacity of LdsRNA to suppress inflammatory mediators in a physiologically relevant model of disc inflammation. By using viral-like RNA molecules, this work highlights how pathways that normally drive antiviral responses can also be used to regulate inflammation. Understanding these mechanisms will provide greater insight into RNA-based strategies for treating inflammatory conditions.