Recent studies have shown that the estrogen receptor I+- (ERI+-), but not ERI2, is involved in the proinflammatory and propruritic responses in cutaneous allergy. In addition, results from our recent study showed that while oral administration of the rather ERI2-selective agonist Bisphenol A exacerbated the respiratory allergic inflammation, the potential inflammatory reaction in the skin was decreased after administration of Bisphenol A. This study aimed to elucidate whether ERI+- and ERI2 are involved in the progression of an allergic airway inflammation. We performed an in vivo experiment using an animal model of allergic airway inflammation using male BALB/c mice to confirm an increase in the proinflammatory response induced by propylpyrazoletriol ( ), an ERI+- agonist, and diarylpropionitrile (DPN), an ERI2 agonist. Oral administration of or DPN showed a significant increase in the inflammation of the lung and infiltration of eosinophils. While the expression of Th2 cytokines such as interleukin 4 (IL-4) and IL-13 was not affected by exposure to or DPN, administration of these agonists significantly increased the expression of IL-33. The mechanism underlying the development of such allergic inflammatory responses was determined by an in vitro study using the human bronchial epithelial cell line (BEAS-2B) and the human eosinophilic leukemia cell line (EoL-1). Activated cells were exposed to or DPN for 24ah, and the cytokine levels were measured. The IL-33 levels in BEAS-2B cells increased significantly after exposure to or DPN. In addition, pretreatment with or DPN increased the expression of IL-8 in activated EoL-1 cells. Our findings indicate that ERI+- and ERI2 are involved in the proinflammatory response in respiratory allergy, and their effects may be mediated by an increase in the expression of IL-33 and infiltration of eosinophils.
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This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.