Melatonin ameliorates lung cell inflammation and apoptosis caused by Klebsiella pneumoniae via AMP-activated protein kinase

Abstract

Klebsiella pneumoniae is a Gram-negative bacterium and the causative agent of several life-threatening nosocomial infections, including pneumonia. K. pneumoniae induces acute lung injury and inflammation in humans that require immediate hospitalization and treatment. Therefore, attenuation of K. pneumoniae-induced inflammation is necessary for the survival of patients. This study investigated the mechanisms by which melatonin abrogated K. pneumoniae-induced inflammation and apoptosis of lung cell lines, HLF-1 and BEAS-2B. Our results showed that in vitro infection of HLF-1 and BEAS-2B cells by K. pneumoniae significantly induced inflammation and apoptosis increased elevated levels of IL-6, CXCL1, CXCL2, and caspase-9 mRNA. However, these effects were abrogated by melatonin treatment. Infection with K. pneumoniae significantly increased the expression of AMP-induced protein kinase (AMPK). Furthermore, AMPK silencing significantly abrogated the suppression of inflammation and apoptosis in melatonin-infected K. pneumoniae lung cells. Melatonin could alleviate K. pneumoniae infection-induced inflammation in three-dimensional lung spheroids. In conclusion, our study demonstrated that melatonin abrogated K. pneumoniae-induced inflammation and apoptosis in lung cells through AMPK. Our study demonstrated the potential of melatonin for therapy against K. pneumoniae infections including pneumonia.