Dexamethasone modulation ofMUC5ACandMUC2gene expression in a generalized model of middle ear inflammation

Abstract

Objective To examine the effect of dexamethasone on basal and pro-inflammatory cytokines induced gel forming mucin expression in human middle ear epithelium culture (HMEEC-1). Methods HMEEC-1 was exposed to pro-inflammatory cytokines, TNF-α and IL-1β to identify optimal mucin induction. The HMEEC-1 was incubated with dexamethasone in the steady state and in the presence of pro-inflammatory cytokine stimulation. Expression of MUC2 and MUC5AC was determined by quantitative PCR. Results Pro-inflammatory cytokines, TNF-α and IL-1β, induced MUC2 and MUC5AC expression in HMEEC-1. Dexamethasone reduced steady state mRNA level of MUC5AC in a time (p<0.05) and dose dependent manner (p<0.0001). MUC2 was effectively suppressed at all time-points tested (p<0.05). Temporal difference between dexamethasone suppression of MUC2 and MUC5AC was demonstrated. Dexamethasone inhibits the pro-inflammatory cytokine induced expression of both MUC2 and MUC5AC. Conclusion This work provides a conclusive picture of the ability of using glucocorticoids to down-regulate mucin gene expression in human middle ear epithelium using a generalizable model of inflammation which is applicable to multiple potential causes of middle ear epithelium mucosal hypertrophy. This data adds to the promising potential of future interventions for patients with chronic otitis media.

RNA Sequencing and Pathways Analyses of Middle Ear Epithelia From Patients With Otitis Media

“…Relative estrogen deficiency may explain male susceptibility to OM 67 . Dexamethasone transcriptionally modulates MUC5AC and MUC2 expression in MEE 68 and has been investigated as a treatment for OM 69 . Oral steroids have been shown to lead to quicker resolution of acute OM when used in conjunction with antibiotics 69 .…”