Changes in expression of neurotrophins and neurotrophic factors in the model of eosinophilic inflammation of the esophageal mucosa

Abstract

AbstractEsophageal sensory and motor nerves contribute to the symptoms of eosinophilic esophagitis, however, the mechanisms of this neural dysfunction are essentially unknown. We addressed the hypothesis that eosinophilic inflammation in the esophagus alters production of the key regulators of neural function neurotrophins and neurotrophic factors. We developed and optimized the model of allergic eosinophilic inflammation of esophageal mucosa induced by localized administration of allergen ovalbumin into the esophagus in ovalbumin-sensitized guinea pigs. We evaluated changes in expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and artemin in esophageal mucosa by quantitative RT-PCR. We found that the administration of ovalbumin into the esophageal wall of sensitized animals induced a massive eosinophilic infiltration restricted to esophageal mucosa (3 ± 1 vs. 97 ± 23 eosinophils per high power filed). This inflammatory response altered the expression profile of selected neurotrophic factors. The BDNF mRNA was increased (to 200%), artemin mRNA was decreased (to 50%) while NGF and GDNF was not changed. We conclude that a strong eosinophilic inflammation can be induced in guinea pigs and alters the expression of neurotrophins and neurotrophic factors. Our findings will aid mechanistic studies of neural dysfunction in eosinophilic esophagitis.