Octreotide activates autophagy to alleviate lipopolysaccharide-induced human pulmonary epithelial cell injury by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

Abstract

Octreotide is a synthetic octapeptide of natural somatostatin. We aimed to investigate the influence of Octreotide on lipopolysaccharide (LPS)-stimulated human pulmonary epithelial cell damage. After stimulated by LPS, BEAS-2B cells were treated with various concentrations of Octreotide. CCK-8 assay and LDH kits were to evaluate cell cytotoxicity. ELISA kits were to analyze the levels of inflammatory factors. TUNEL staining was to measure cell apoptosis. Western blot assay was used to assess the expression of apoptosis-related proteins, autophagy-related proteins and AKT/mTOR signaling-related proteins. Then, 3-methyladenine (3-MA) was adopted for treating BEAS-2B cells to determine its effects on inflammation and apoptosis. Afterward, adding AKT agonist (SC79) or mTOR antagonist (rapamycin) to explore the impact of Octreotide on autophagy. Results revealed that Octreotide notably enhanced cell viability and reduced LDH activity. The levels of inflammatory factors were significantly decreased following Octreotide treatment. Additionally, Octreotide attenuated the apoptotic capacity of LPS-induced BEAS-2B cells, led to the up-regulation of Bcl-2 protein level while cut down the protein levels of Bax and cleaved caspase3. Remarkably, the expression of autophagy-related protein LC3II/I and Beclin1 was elevated after Octreotide administration. Importantly, the suppressive effects of Octreotide on the inflammation and apoptosis of LPS-induced BEAS-2B cells was abrogated by 3-MA. Further experiments suggested that Octreotide downregulated p-AKT and mTOR expression in LPS-stimulated BEAS-2B cells. SC79 addition inhibited autophagy, evidenced by downregulated LC3II/I and Beclin1 expression while rapamycin presented the opposite effects. To conclude, Octreotide activates autophagy to alleviate LPS-induced pulmonary epithelial cell injury by inhibiting the AKT/mTOR signaling.

Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway

“…Autophagy, a crucial biological process involved in the degradation and removal of detrimental proteins and organelles within cells via autophagosome formation, 20 plays a pivotal role in maintaining cellular viability. Autophagy is constitutively present at basal levels under physiological conditions and plays a pivotal role in maintaining intracellular homeostasis.…”