Kukoamine A inhibits C‐C motif chemokine receptor 5 to attenuate lipopolysaccharide‐induced lung injury

Abstract

The aim of this study was to elucidate the mechanism underlying the effects of Kukoamine A (KuA) treatment on endotoxin-induced lung injury/inflammation. The study was performed in lipopolysaccharide (LPS)-exposed mouse models of lung injury and LPS-induced alveolar epithelial cell model. Relevant kits were used to detect levels of inflammation-related indicators, oxidative stress indicators, and mitochondrial function. Hematoxylin and eosin staining was to detect lung injury. Then, C-C motif chemokine receptor 5 (CCR5) overexpression plasmid was transfected into alveolar epithelial cells to investigate the mechanism of KuA in lung injury. The results showed that LPS induction increased the expression of inflammatory factors, oxidative stress markers, and mitochondrial dysfunction in both animal and cellular models. In the mouse model, KuA treatment improved lung tissue injury, decreased wet-to-dry ratio and MPO levels, reduced the expression of inflammatory factors, and ameliorated oxidative stress and mitochondrial dysfunction. The protective effect of KuA in the cell model remained whereas was markedly reversed after CCR5 overexpression. Taken together, KuA might improve LPS-induced lung injury by inhibiting CCR5. This might also provide a novel theory for KuA in the treatment of lung injury.

Characterization of Biological Properties of Individual Phenolamides and Phenolamide-Enriched Leaf Tomato Extracts

“…Moreover, when added one hour before LPS, the three phenolamides were able to set differentiated THP-1 cells in an anti-inflammatory state that afterwards render them less sensible to the LPS pro-inflammatory stimulus. The ability of Kuk_A to counteract LPS-induced proinflammation was very recently described by Liu et al and Wang et al in other cells than macrophages [ 46 , 47 ]. Liu et al used an in vivo mouse model of lung injury with LPS, and an in vitro model of alveolar epithelial cells preincubated with LPS.…”

“…Liu et al used an in vivo mouse model of lung injury with LPS, and an in vitro model of alveolar epithelial cells preincubated with LPS. In both models, they demonstrated that Kuk_A decreased the expression of inflammatory factors and oxidative stress markers that were dependent of CCR5 inhibition [ 46 ]. In the same manner, Wang et al demonstrated that Kuk_A added in cell culture medium of nucleus pulposus cells preincubated with LPS, attenuated LPS-induced apoptosis, extracellular matrix degradation, and inflammation.…”