Korean J Intern Med.  2020 Sep;35(5):1229-1237. 10.3904/kjim.2019.105.

N-acetylcysteine decreases airway inflammation and responsiveness in asthma by modulating claudin 18 expression

• Lee PH
• Hong J
• Jang AS

• KMID: 2505632
• DOI: http://doi.org/10.3904/kjim.2019.105

Abstract

Background/Aims
N-acetylcysteine (NAC) affects signaling pathways involved in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and the inflammatory response. However, it is not known how the signal mechanism for tight junctional protein claudin (CLDN) 18 is regulated in asthma patients.
Methods
To investigate the effects of NAC on CLDN18 expression in a mouse model of asthma, and to assess plasma levels of CLDN18 in asthma patients. A murine model of asthma induced by ovalbumin (OVA) was established using wild-type BALB/c female mice, and the levels of CLDNs, phosphorylated-pyruvate dehydrogenase kinase 1 (p-PDK1), and protein kinase B (Akt) pathway proteins following NAC treatment were examined by Western blotting and immunohistochemistry. In addition, the plasma levels of CLDN18 were evaluated in asthmatic patients and control subjects.
Results
NAC diminished OVA-induced airway hyper-responsiveness and inflammation. Levels of CLDN18 protein were higher in lung tissue from OVA mice than tissue from control mice, and were increased by treatment with NAC or dexamethasone. Treatment with NAC or dexamethasone decreased the OVA-induced increase in interleukin-1α protein levels. Although treatment with NAC increased OVA-induced p-PDK1 protein levels, it decreased phosphorylated Akt (pAkt)/Akt levels. Soluble CLDN18 levels were lower in patients with asthma than in controls and were correlated with the percentage of neutrophils, forced expiratory volume in 1 second (FEV1)/forced vital capacity % (FVC%) and FEV1%.
Conclusions
CLDN18 plays a role in the pathogenesis of asthma and NAC diminishes airway inflammation and responsiveness by modulating CLDN18 expression.

Keyword

Asthma; Claudin 18; N-acetylcysteine; Plasma; Tight junction