科研之友
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摘要
Resistin-like molecule (Relm)-alpha is a secreted, cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-alpha, and Relm-alpha. Although resistin was initially defined based on its insulin-resistance activity, the family members are highly induced in various inflammatory states. Earlier studies implicated Relm-alpha in insulin resistance, asthmatic responses, and intestinal inflammation; however, its function still remains an enigma. We now report that Relm-alpha is strongly induced in the esophagus in an allergen-challenged murine model of eosinophilic esophagitis (EoE). Furthermore, to understand the in vivo role of Relm-alpha, we generated Relm-alpha gene-inducible bitransgenic mice by using lung-specific CC-10 promoter (CC10-rtTA-Relm-alpha). We found Relm-alpha protein is significantly induced in the esophagus of CC10-rtTA-Relm-alpha bitransgenic mice exposed to doxycycline food. The most prominent effect observed by the induction of Relm-alpha is epithelial cell hyperplasia, basal layer thickness, accumulation of activated CD4(+) and CD4(-) T cell subsets, and eosinophilic inflammation in the esophagus. The in vitro experiments further confirm that Relm-alpha promotes primary epithelial cell proliferation but has no chemotactic activity for eosinophils. Taken together, our studies report for the first time that Relm-alpha induction in the esophagus has a major role in promoting epithelial cell hyperplasia and basal layer thickness, and the accumulation of activated CD4(+) and CD4(-) T cell subsets may be responsible for partial esophageal eosinophilia in the mouse models of EoE. Notably, the epithelial cell hyperplasia and basal layer thickness are the characteristic features commonly observed in human EoE.
- 出版日期2014-9-1
