Purchase this article with an account.
David A Sullivan, Yang Liu, Wendy R Kam, Raheleh Rahimi Darabad, Afsun Sahin; Androgen suppression of proinflammatory gene expression in human meibomian gland epithelial cells.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2255.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We discovered that dihydrotestosterone (DHT) decreases the ability of lipopolysaccharide, a bacterial toxin, to stimulate the secretion of leukotriene B4, a potent proinflammatory mediator, by immortalized human meibomian gland epithelial cells (IHMGECs; Sahin A et al, Arch Ophthalmol 2012;130:1013-1018). We hypothesize that this hormone action reflects an androgen suppression of proinflammatory gene activity in these cells. Our goal was to test this hypothesis.
Confluent IHMGECs were cultured for 2.3 days in media containing charcoal-stripped serum and vehicle or 10 nM DHT. Cells (n = 3 wells/treatment group) were then processed for RNA isolation and the analysis of gene expression by using Illumina BeadChips, background subtraction, cubic spline normalization and Geospiza software.
Our results demonstrate that DHT significantly suppresses the expression of 67 immune response genes in IHMGECs, including those related to innate and adaptive immune responses, antigen processing and presentation, T cell mediated immunity, chemotaxis, and the production, binding, activity and signaling of cytokines and/or chemokines. As examples, DHT downregulates genes encoding IL-1 beta and IL-8. In contrast, DHT enhances the expression of genes for IL-1 receptor antagonist and defensin beta 1 in IHMGECs.
Our findings support our hypothesis that androgens suppress proinflammatory gene expression in IHMGECs. This hormone effect may contribute to the typical absence of inflammation within the human meibomian gland.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only