Effects of Ammonium Chloride on Ozone-induced Airway Inflammation: the Role of Slc26a4 in the Lungs of Mice
10.3346/jkms.2020.35.e272
- Author:
Jong-Uk LEE
1
;
Hyeon Ju LEE
;
Ji-Na KIM
;
Min Kyung KIM
;
Sung Roul KIM
;
Hun-Soo CHANG
;
Choon-Sik PARK
;
Jong-Sook PARK
Author Information
1. Division of Allergy and Respiratory Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Publication Type:Original Article
- From:Journal of Korean Medical Science
2020;35(32):e272-
- CountryRepublic of Korea
- Language:0
-
Abstract:
Background: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.
Methods: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.
Results:The levels Slc26a4 protein and mRNA significantly increased in lung tissues from Day 7 to Day 21 of O3exposure, 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. NH4 Cl treatment also significantly attenuated the O3 -induced increases in IFN-γ, TNF-α, IL-17, IL-1β, and p20-activated caspase-1.
Conclusion: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. NH4 Cl shows a potential as a therapeutic agent for controlling O3 -induced airway inflammation and epithelial damage by modulating Slc26a4 expression.
