Dupilumab antagonizes the stimulatory effects of IL-13 on mucin production by human bronchial epithelium cells.

Résumé fourni par la source

Chronic obstructive pulmonary disease is a progressive respiratory disease with chronic inflammation and mucin overproduction. Dupilumab is a monoclonal antibody clinically approved for treating allergic diseases that inhibits signalling of interleukin-4 (IL-4) and 13 (IL-13). IL-4 and IL-13 are mediators of inflammation and mucin stimulators. This study aims to explore the pharmacological effects of Dupilumab in regulating mucin production in response to IL-13 stimulation. Human bronchial epithelial cells (BEAS-2B) were seeded and starved for 24h prior the pharmacological treatments, exposed for 1h to dupilumab before stimulation with IL-13 for 24h. MUC5AC protein was measured on supernatant via ELISA, while MUC5AC RNA was extracted from cells lysates and assessed by RT-qPCR. IL-13 elicited a robust and concentration dependent stimulation of MUC5AC production both at mRNA and protein level, with similar high potency values of 11.07±0.76 and 10.79±0.8, respectively. Dupilumab up to 10 nM didn’t modify MUC5AC mRNA while induced a small reduction of basal MUC5AC protein levels. When challenged against the stimulatory effect of IL-13, Dupilumab caused a concentration dependent rightward shift of the concentration response curve to IL-13 showing pM potency (pA2) of 11.00±0.89 on mRNA and of 10.64±0.81 on protein, similar to as described in literature (1,2) These results suggest that IL-13 is an important stimulus for mucin production by bronchial epithelial cells. Moreover, the potent antagonist action of Dupilumab against IL-13 showed the involvement of the IL-4 receptor alpha subunit in the mucin stimulatory effect of the cytokine. IL-13 / IL-4 Rα/IL-13Rα1 signalling pathway may be view as target for the development of innovative treatments for conditions link to mucin overproduction

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