Endocrine Abstracts (2019) 65 P204 | DOI: 10.1530/endoabs.65.P204

Glucocorticoid regulation of the PEPITEM pathway

Ailbhe Ni Chosgora, Sophie Hopkin, Rowan Hardy, Ed Rainger & Myriam Chimen


University of Birmingham, Birmingham, UK


Dysregulated recruitment of leukocytes across endothelial cells into target tissues is a hallmark of the pathology of most chronic inflammatory diseases (CIDs). We have identified a novel homeostatic pathway that regulates T-cell migration during inflammation. The pathway is impaired in patients with CIDs such as type-1-diabetes and rheumatoid arthritis (RA), and is also attenuated in the elderly. The dysregulation of this pathway across all conditions is caused by a lower level of adiponectin receptors (AdipoRs) on B-cells, which leads to less secretion of PEPITEM (PEPtide Inhibitor of Trans-Endothelial Migration) in response to adiponectin. It is therefore important to understand how this pathway is regulated to potentially develop therapies that will re-balance T-cell recruitment during inflammation. We hypothesise that changes in AdipoRs expression on B-cells is caused by a common process across these distinct CIDs. Here, we aimed to determine whether glucocorticoids such as cortisol and their associated modulating enzymes, 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 2), regulate the PEPITEM pathway. Isolated B-cells were cultured in the presence of cortisol and other leukocytes for 48 h and the expression of AdipoR1/2 was measured using flow cytometry. Expression of 11β-HSD1/2, AdipoR1/2, and glucocorticoid associated genes was measured using qPCR. We observed up-regulation of AdipoR1/2 on B-cells in the presence of cortisol and monocytes but not on B-cells alone. In addition, we observed a reduction in the expression of AdipoR1/2 in the 11β-HSD1 knock-out mouse. The expression of 11β-HSD1 is very low in B-cells but is increased in the presence of stimulatory signals such as Interleukin-4. Our preliminary data indicate that patients with RA have lower expression of 11β-HSD1 than in gender and age-matched healthy controls. Our data indicate a potential role of cortisol in the regulation of the PEPITEM pathway via a cross-talk with monocytes and a potential role for 11β-HSD1.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts