Aquaporin-5 (AQP5) is a water-selective channel protein that is expressed in submucosal glands and alveolar epithelial cells in the lungs. Recent studies have revealed that AQPs regulate not only water metabolism, but also some cellular functions such as cell growth and migration. Here, we report the role of AQP5 in inflammatory responses. In MLE-12 cells, knockdown of AQP5 using siRNA (10-50 nM) attenuated TNF-alpha-induced expression of keratinocyte chemoattractant (KC) mRNA and protein. Conversely, in NIH-3T3 cells, overexpression of AQP5 increased KC expression, NF-kappa B activation, and ERR phosphorylation. The AQP5-induced increase of KC expression was diminished by treatment with ERK inhibitors. Taken together, we propose a new function of AQP5 as an inflammatory signal potentiator, which may be mediated by increased activation of ERK and NF-kappa B. (C) 2014 Elsevier Inc. All rights reserved.