Effects of Ammonium Chloride on Ozone-induced Airway Inflammation: the Role of Slc26a4 in the Lungs of Mice.

Exposure to ozone (O₃) induces neutrophilic inflammation and goblet cell hyperplasia in humans and experimental animals. Because the solute carrier family 26-member 4 (Slc26a4; pendrin) gene induces mucin production and intraluminal acidification in the airways, it was hypothesized to be a key molecule in O₃-induced airway injury. Thus, we evaluated the role of Slc26a4 and the protective effects of ammonium chloride (NH₄Cl) in O₃-induced airway injury in mice. Six-week-old female BALB/c mice were exposed to filtered air or O₃ for 21 days (2 ppm for 3 hr/day). NH₄Cl (0, 0.1, 1, and 10 mM) was administered intratracheally into the airways. Airway resistance was measured using a flexiVent system, and bronchoalveolar lavage fluid (BALF) cells were differentially counted. Slc26a4 and Muc5ac proteins and mRNA were measured via western blotting, real-time polymerase chain reaction, and immunostaining. Tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-17, IL-1β, and caspase-1 were analyzed via western blotting. The levels Slc26a4 protein and mRNA significantly increased in lung tissues from Day 7 to Day 21 of O₃ exposure, with concomitant increases in lung resistance, numbers of goblet cells in lung tissues, and inflammatory cells and thiocyanate (SCN-) levels in BALF in a time-dependent manner. Treatment with NH₄Cl significantly reduced these changes to levels similar to those of sham-treated mice, with a concomitant reduction of Slc26a4 proteins in lung lysates and SCN- levels in BALF. Slc26a4 protein was co-expressed with muc5ac protein in the bronchial epithelium, as indicated by immunofluorescence staining. NH₄Cl treatment also significantly attenuated the O₃-induced increases in IFN-γ, TNF-α, IL-17, IL-1β, and p20-activated caspase-1. Slc26a4 may be involved in O₃-induced inflammatory and epithelial changes in the airways via activation of the inflammasome and the induction of IL-17 and IFN-γ. NH₄Cl shows a potential as a therapeutic agent for controlling O₃-induced airway inflammation and epithelial damage by modulating Slc26a4 expression. © 2020 The Korean Academy of Medical Sciences.

Citation

Jong Uk Lee, Hyeon Ju Lee, Ji Na Kim, Min Kyung Kim, Sung Roul Kim, Hun Soo Chang, Choon Sik Park, Jong Sook Park. Effects of Ammonium Chloride on Ozone-induced Airway Inflammation: the Role of Slc26a4 in the Lungs of Mice. Journal of Korean medical science. 2020 Aug 17;35(32):e272

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PMID: 32808511

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