RESUMEN
Background: Acute lung injury (ALI) is a serious condition. Inflammation plays a crucial role in the pathogenesis of ALI. Cupping, as a part of traditional Chinese medicine, is still a popular complementary and alternative therapy for a variety of ailments including respiratory diseases. However, reliable scientific data about cupping therapy are scarce. Adenosine, a purine nucleoside produced under metabolic stress by the action of extracellular ectonucleotidases (i.e. CD39 and CD73), can attenuate ALI through the A2BAR receptor. The aim of this study was to investigate the protective effect of cupping in a rat model of ALI and the role of adenosine in it. Methods: Male adult rats were subjected to ALI by intratracheal LPS instillation (0.3 mg/kg). Immediately after intratracheal LPS instillation, vacuum pressure was applied to a sanitized plastic bell cup on the back of the rat by suction for 10 min. Pulmonary injury and inflammation were assessed at 4 h after LPS challenge. The role of adenosine and A2BAR in cupping's protection after LPS instillation were evaluated. Results: Cupping alleviated LPS-induced lung injury, reduced inflammation and inhibited NF-kB activation in rats. Cupping upregulated CD39 and CD73 mRNA expression of the skin tissue at the cupping site and increased circulating levels of adenosine. Administration of PSB1115, a specific adenosine A2BAR receptor antagonist, abolished cupping's beneficial effects in LPS-induced ALI. Conclusions: Cupping attenuates lung inflammation and injury through the adenosine/A2BAR pathway. The current study provides evidence-based information about cupping therapy in ALI.
RESUMEN
Alcoholic hepatitis is a serious form of liver damage. Inflammation is a key factor in alcoholic hepatitis and plays a key role in the progression of alcoholic liver disease. Adenosine receptor A2B (A2BAR) is a member of the adenosine receptor family and generally considered to be a negative regulator of the inflammatory response. We found that A2BAR was the most highly expressed adenosine receptor in ETOH-fed mouse liver tissue and was also highly expressed in primary Kupffer cells and ETOH-induced RAW264.7 cells. In addition, injection of BAY 60-6583 stimulated A2BAR, induced upregulation of the expression levels of cAMP, and reduced ETOH-induced steatosis and inflammation in mice. At the same time, knockdown of A2BAR in vitro increased the inflammatory response in RAW264.7 cells triggered by ETOH. After knockdown of A2BAR in vitro, the release of the inflammatory cytokines IL-6, IL-1ß and TNF-α was increased. After overexpression of A2BAR in vitro, the cAMP level was significantly increased, PKA expression was increased, the expression of phosphorylated proteins in the NF-kB signal transduction pathway was significantly affected, and the expression of the key phosphorylated protein p-P65 was decreased. However, after the simultaneous overexpression of A2BAR and inhibition of PKA, the expression of the key phosphorylated protein p-P65 was still significantly decreased. In addition, after the expression of A2BAR increased or decreased in RAW264.7 cells, AML-12 cells were cultured in the supernatant of RAW264.7 cells stimulated by ETOH, and the apoptosis rate was significantly changed by flow cytometry. These results suggest that A2BAR can reduce alcoholic steatohepatitis by upregulating cAMP levels and negatively regulating the NF-kB pathway. Overall, these findings suggest the significance of A2BAR-mediated inflammation in alcoholic liver disease.