Resveratrol alleviates Staphylococcus�aureus pneumonia by inhibition of the NLRP3 inflammasome

Abstract

Abstract. Staphylococcus aureus (S. aureus) causes a wide variety of infections, including S. aureus pneumonia. Resveratrol, a natural polyphenolic compound contained in several plant species, exerts various activities, including anti-bacterial and pulmonary protective activities. The aim of the present study was to evaluate the protective effect of resveratrol on a murine model of S. aureus pneumonia and to elucidate the underlying mechanisms. It was found that resveratrol significantly reduced S. aureus-induced mortality, ameliorated lung injury and decreased cytokine levels in the bronchoalveolar lavage fluid and lung tissue of S. aureus infected-mice. In addition, reverse-transcription quantitative polymerase chain reaction and western blot assays showed that resveratrol markedly decreased the mRNA and protein expression of nucleotide-binding domain and leucine-rich repeat containing gene family pyrin domain containing 3 protein (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain and caspase-1. These results demonstrated that resveratrol significantly alleviates S. aureus pneumonia in mice, the possible underlying mechanism of which is associated with the inhibition of the NLRP3 inflammasome. The present study suggested that resveratrol is a potentially useful agent for the treatment of S. aureus pneumonia and S. aureus-induced infectious diseases.

Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury

“…Thus, therapeutic targeting of NLRP3, NLRC4, and NLRP4 inflammasome during Gram-positive bacteria-induced severe pneumonia responsible for ALI may prove beneficial to the host. An experimental study has shown the beneficial effects (inhibition of ALI, decrease in pro-inflammatory cytokines levels, and decrease in the mortality) of resveratrol during K. pneumoniae -induced pneumonia through the NLRP3 inflammasome inhibition ( 100 ). NLRC4 activation during Gram-negative bacterial ( K. pneumoniae, P. aeruginosa ) pneumonia proves beneficial to the host via producing IL-1β, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs ( 101 ).…”

Health benefits of resveratrol administration

“…Furthermore, by reducing the expression of perilipin 5, resveratrol accelerates lipid hydrolysis in brown adipose tissue, which may cause a decrease in weight and myocardial steatosis of heart tissue (Mehdi et al, 2018). Resveratrol also exhibits antimicrobial activity against Haemophilus influenzae (Euba et al, 2017), Escherichia coli (Subramanian et al, 2014), Propionibacterium acnes (Taylor et al, 2014), and Staphyloccocus aureus (Wu & Huang, 2017). Toniolo et al (2018) observed that supplementation with 0.04% resveratrol for six months also improves the resistance to fatigue and functional-mechanical properties of skeletal muscles in aged mice.…”

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases

“…It is well-established that Nod-like receptor (NLR) family pyrin domain containing-3 (NLRP3) inflammasome is a caspase-1-triggering multiprotein complex that plays an essential role in the progression of inflammatory diseases via regulating the release of cytokines. The previous report demonstrated that resveratrol improved S. aureus -induced pneumonia in mice by significantly decreasing the mRNA and protein expression of Caspase-1, NLRP3 and apoptosis-associated speck-like protein (ASC) ( Wu & Huang, 2017 ). It has been well documented that NF-kB expression and relative NLRP3 targets are regulated by p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinases 1 and 2(JNK1/2) and activator protein 1 (AP-1) signaling pathways in various cell types.…”

“…( M. officinalis , Houpu in Chinese), Belamcanda chinensis (L.) Redouté ( B. chinensis , Shegan in Chinese) and Panax notoginseng (Burkill) F. H. Chen ex C. H. ( P. notoginseng , Sanqi in Chinese) have been applied as common herbal medicines of traditional Chinese prescriptions for treating lung disease, and interestingly, all of these herbal medicines contain resveratrol ( Table 1 ). Many studies illustrated the promising therapeutic effects of resveratrol against lung diseases mainly by decreasing oxidant stress, suppressing free radicals like reactive oxygen species (ROS) and inhibiting inflammatory responses ( Wu & Huang, 2017 ). Furthermore, resveratrol has been characterized with anti-microbial, neuroprotective, anti-aging, cardioprotective and anti-cancer activities both in vivo and in vitro ( Lee et al, 2018 , Li et al, 2018 ).…”