Resveratrol ameliorates Serratia marcescens-induced acute pneumonia in rats

Chia-Chen Lu^*^,1, Hsin-Chih Lai^,1, Shang-Chen Hsieh^,1 and Jan-Kan Chen^*^,2

^* Department of Physiology, College of Medicine, and
Graduate Institute of Medical Biotechnology and Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Kweishan, Taiwan, Republic of China; and
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taiwan, Republic of China

² Correspondence: Department of Physiology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan, Republic of China, 333. E-mail: jkc508{at}mail.cgu.edu.tw

ABSTRACT

Serratia marcescens is an important nosocomial pathogen, whichhas been especially problematic as a cause of hospital-acquiredpneumonia in the past two decades. Treatment of S. marcescens-relatedinfections has been limited by emergence of multiple drug-resistantstrains. Thus, the development of alternative agents for theprevention and treatment of Serratia infection is urgently needed.Resveratrol (RSV) is a compound with diverse biological effectsincluding anti-cancer, anti-inflammation, anti-diabetes, andcancer chemoprevention. Whether RSV has in vivo prophylacticor therapeutic potential against infection remains uncharacterized.In the present study, we used a murine acute pneumonia modelinitiated by intratracheal application of S. marcescens to evaluatewhether RSV possesses anti-infection properties. We showed thatpretreatment with RSV for 3 days markedly increased alveolarmacrophage infiltration, elevated NK cell activity, and decreasedbacterial burden in the infected lung with a subsequent decreasein mortality. These effects were associated with significantlyless-severe inflammatory phenotypes in lung tissue and bronchoalveolarlavage fluid, including reduced neutrophil infiltration of thelungs, reduced phagocytosis activity, and reduced secretionof cytokines such as TNF- ${alpha}$ , IL-1β, and IL-6. To furthercharacterize the underlying mechanism responsible for theseeffects of RSV, LPS derived from S. marcescens was used to induceacute pneumonia in rats, with or without RSV pretreatment. RSVwas shown to ameliorate acute pneumonia via inhibition of theNF- ${kappa}$ B signaling pathway, including inhibition of I ${kappa}$ B ${alpha}$ phosphorylationand subsequent NF- ${kappa}$ B activation. These findings suggest thatRSV might be beneficial as a prophylactic treatment in patientsat risk of an episode of S. marcescens-induced acute pneumonia.

Key Words: anti-inflammation • NF- ${kappa}$ B