EPITHELIX

Goblet Cell Metaplasia

Aim:

The aim of this assay is to evaluate compound efficacy to block or to reverse goblet cell metaplasia.

Model:

MucilAir™ is treated during two weeks with IL-13 at different concentrations, ranging from 0.3 to 30 ng/ml. Using in situ Alcian Blue staining, as well as histological analysis, an increased goblet cell density after 14 days of IL-13 treatment, in a dose-response manner is observed. Furthermore, ELISA analysis reveals a concomitant increase of Eotaxin-3 released in the culture media in function of IL-13 concentration. Interestingly, the ciliated cells are still present, and the muco-ciliary clearance is still functional, despite of an over-production of mucus.

anti-Muc-5Ac-antibody
x anti-Muc-5Ac-antibody


Figure: The figures depict paraffin sections stained with anti-Muc-5Ac antibody from 2 batches of MucilAir

Mucus cells
x Mucus cells
ELISA Quantification of Eotaxin
x ELISA Quantification of Eotaxin

Figure: Left: Percentage of the mucus cells over the total surface was measured using Software ImageJ, showing a dose-dependent increase of the goblet cell density induced by IL-13 at Day 14.
Right: ELISA Quantification of Eotaxin-3, a chemokine induced by IL-13 at Day 14.


Application

Respiratory allergy as well as asthma is characterized by TH-2 cytokine-mediated immune response in which IL-2, 3, 5, and 13 play an important role. Treated with neutralizing anti-IL-13 monoclonal antibody, the health condition of several asthmatic patients was significantly improved, suggesting that targeting the TH-2 cytokines is a promising therapeutic option. This assay allows assessing and ranking the efficacy of drugs blocking the IL-13 signaling pathway.

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