Low MicroRNA Activity Characterizes Inflamed Lung Tissues

A recent study examined the interaction between a specific microRNA (miRNA) and the activity of the inflammatory cytokine interleukin 13 (IL-13).

IL-13 induces many features of allergic lung disease, including airway hyperresponsiveness, goblet cell metaplasia, and mucus hypersecretion, which all contribute to airway obstruction. IL-13 also induces secretion of chemokines that are required for recruitment of allergic effector cells to the lung. While no studies have yet directly implicated IL-13 in the control of human diseases, many polymorphisms in the IL-13 gene have been shown to confer an enhanced risk of atopic respiratory diseases such as asthma.

In the current study, investigators at the Cincinnati Children's Hospital Medical Center (Ohio, USA) examined the effect that stimulation of IL-13 activity has on microRNAs, particularly miR-375. To this end, they performed experiments using cultures of human esophageal squamous and bronchial columnar epithelial cells as well in lung tissue from a line of IL-13 transgenic mice.

They reported in the March 28, 2012, online edition of the journal Mucosal Immunology that IL-13 induced changes in epithelial gene and protein expression including the consistent downregulation of miR-375 in IL-13 stimulated human esophageal squamous and bronchial epithelial cells. MiR-375 was downregulated in the lung tissue of the IL-13 transgenic mice. Analysis of miR-375 levels in a human disease characterized by IL-13 overproduction - the allergic disorder eosinophilic esophagitis (EE) - revealed downregulation of miR-375 in EE patient samples compared with control patients. Low levels of miR-375 expression levels indicated disease activity. MiR-375 levels normalized with remission, and were inversely correlated with the degree of allergic inflammation.

“The identification of a microRNA that regulates IL-13-induced changes and inflammatory pathways is a significant advancement for the understanding and future treatment of allergic disease,” said senior author Dr. Marc E. Rothenberg, professor of allergy and immunology at Cincinnati Children's Hospital Medical Center. “MiR-375 is proof of principle that microRNAs are involved in fine-tuning IL-13-mediated responses, which opens up a set of new possibilities for novel therapeutic targets for treatment of allergic disease.”

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Cincinnati Children's Hospital Medical Center