Cortisol-Responsive regulation of RASGRP1 in lymphoblastoid cells from individuals with bipolar disorder

Bipolar Disorder (BD) is a complex psychiatric disorder, characterised by recurrent episodes of mania and depression, and is associated with the dysregulation of stress hormone signalling, immune and inflammatory pathways. However, limited information is currently available on the effects of stress hormones on immune and inflammatory pathways in BD. Ras guanyl releasing protein 1 (RASGRP1) is a pro-inflammatory guanine nucleotide exchange factor involved in Ras-MAPK signalling. Cortisol exerts well-known anti-inflammatory effects; we therefore hypothesized that cortisol exposure would regulate RASGRP1 expression. This study, therefore, examined the impact of cortisol on RASGRP1 transcriptional and translational expression across BD subtypes in lymphoblastoid cell lines derived from BD and non-BD individuals. We observed differential responses to cortisol among the cell lines. Specifically, at the level of transcription expression was elevated in BD II cortisol-treated cells at basal levels vs. stress induced levels of cortisol. Concurrently, RASGRP1 protein was detected only in BD II cells treated with basal levels of cortisol. No protein was detected in untreated cells or those exposed to stress-induced levels of cortisol. RASGRP1 expression is responsive to cortisol in a concentration-dependent manner.