The goal of this laboratory study is the examine the effect of mepolizumab drug on the health and function of the cells lining the human nasal airways in vitro cell culture derived from patients with chronic rhinosinusitis with nasal polyposis. The main questions the study aims to study are: 1. To see what mepolizumab does to suppress inflammation of the human cells. 2. To see what mepolizumab does to maintain barrier integrity of epithelial cells
The investigators hypothesize that anti-IL5 treatment will promote epithelial cell function by inhibition of Type 1 and innate immune mediated inflammation and epithelial-mesenchymal transition resulting from IL5 induction. Aim 1. To test the hypothesis that anti-IL5 therapy results in inhibition of epithelial cell dysfunction including epithelial derived inflammatory responses and barrier dysfunction, the investigators will examine the effect of in vitro anti-IL5 mepolizumab exposure of human primary nasal epithelial cells from chronic rhinosinusitis with nasal polyposis on Type 1, Type 2 and innate immune inflammatory markers, and markers of epithelial cell barrier function. Aim 2. To examine the effect of mepolizumab to broadly modulate the expression of Type 2, Type 1, Type 3, and innate immune inflammatory gene responses in human nasal airway epithelial cells, the investigators will perform high throughput RNA sequencing on IL5 primed differentiated human primary nasal epithelial cells exposed to the presence and absence of mepolizumab in vitro cell culture which are derived from patients with chronic rhinosinusitis with nasal polyposis. These studies will provide an unbiased approach to identification of biomarkers resulting from anti-IL5 treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
8
In vitro exposure of human nasal epithelial cells to mepolizumab
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States
RECRUITINGJohns Hopkins Hospital
Baltimore, Maryland, United States
RECRUITINGChange in Type 1 inflammatory markers (ng/mL)
IL8 cytokine mRNA and protein expression
Time frame: 0 to 48 hours
Change in Type 2 inflammatory markers (ng/mL)
IL5 and thymic stromal lymphopoietin cytokine mRNA and protein expression
Time frame: 0 to 48 hours
Change in Innate immune inflammatory markers (ng/mL)
IL1 receptor mRNA and protein expression
Time frame: 0 to 48 hours
Change in epithelial barrier function protein expression (ng/mL)
E-cadherin
Time frame: 0 to 48 hours
Change in epithelial integrity markers (staining intensity units)
alpha-smooth muscle actin protein expression
Time frame: 0 to 48 hours
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