The effect of androgens on proinflammatory cytokine secretion from human ocular surface epithelial cells

Abstract

Purpose: The purpose of this study is to explore the effects of dihydrotestosterone (DHT) on lipopolysaccharide (LPS)-induced proinflammatory cytokine release in human ocular surface epithelial cells exposed to LPS and LPS-binding protein (LBP). Methods: Immortalized human corneal, conjunctival, and meibomian gland epithelial cells were cultured in keratinocyte-free medium. After confluency, they were exposed to a stratification medium Dulbecco's modified Eagle medium (DMEM)/F12 in the presence of fetal bovine serum and were exposed to vehicle, LPS + LBP, or DHT. Culture media were processed for multiplex-bead analysis of specific proinflammatory cytokines including interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-8, IL-6, IL-10, IL-1 beta, vascular endothelial growth factor (VEGF)-A. Cytokine concentrations were compared by analysis of variance with Tukey post hoc testing. p Results: The results are LPS + LBP-induced the secretion of IFN-gamma, IL-6, IL-10, IL-1 beta, VEGF-A cytokines in corneal epithelial cells; TNF-alpha, IL-2, IL-8, IL-6, IL-1 beta, VEGF-A cytokines in conjunctival epithelial cells; and IL-8, IL-6, IL-1 beta, VEGF-A cytokines in meibomian gland epithelial cells. When these LPS + LBP-stimulated cells were exposed to DHT for 2 days, it was found that DHT suppressed the secretion of IL-6, IL-10, IL-1 beta, VEGF-A cytokines in corneal epithelial cells; TNF-alpha, IL-6, IL-1 beta, VEGF-A cytokines in conjunctival epithelial cells; and IL-6, IL-1 beta, VEGF-A cytokines in meibomian gland epithelial cells. Conclusion: LPS + LBP is shown to induce the secretion of certain proinflammatory cytokines from ocular surface and adnexal epithelial cells. DHT showed anti-inflammatory activity by suppressing some of those cytokines in these cell lines.