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Systemic inflammatory response syndrome is a pathophysiological inflammatory response mediated largely by tumor necrosis factor-α (TNF-α), in response to infectious or non-infectious stimuli. TNF-α secretion in response to bacterial lipopolysaccharide (LPS) is regulated in part by disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). Therefore, the present study aimed to identify an effective inhibitor of ADAM17, in order to control inflammation and associated processes. In the present study, a lentiviral vector expressing short hairpin (sh)RNA targeting the ADAM17 gene was constructed. U937 cells were infected with the lentivirus and stimulated with LPS. ADAM17 expression was assessed by western blotting and TNF-α secretion was assessed by ELISA analysis. The lentivirus was additionally tested in vivo in a mouse model of endotoxemia and sTNF-α expression was assessed by flow cytometry in peritoneal macrophages. In vitro, the ADAM17 shRNA lentivirus reduced ADAM17 expression, and prevented TNF-α maturation in U937 cells. In vivo, mice exposed to the ADAM17 shRNA lentivirus prior to LPS-induced endotoxemia exhibited fewer signs of inflammation and less tissue damage compared with the control mice. In conclusion, the present study successfully constructed a shRNA lentiviral vector targeting the ADAM17 gene that exhibited apparent in vitro and in vivo effects on TNF-α processing in response to an LPS challenge. The results of the present study may aid the design and improvement of drugs designed to inhibit the function of ADAM17, and suggested a novel means of controlling inflammation and associated processes.

Disintegrin and metalloproteinase domain-containing proteins (ADAMs) have been implicated in cell adhesion, signaling and migration. The aim of the present study was to identify key members of the ADAM protein family associated with the metastasis of gastric cancer and to evaluate their clinical significance. A total of 193 patients with gastric cancer and positive lymph node metastasis were enrolled. Key members of the ADAM family associated with lymph node metastasis were identified. The correlations between survival times and the clinicopathological features of patients were investigated. Furthermore, ADAM17 expression in gastric cancer cells with different metastatic potentials was determined. ADAM17 was overexpressed in BGC-823 cells and suppressed in SGC-7901 cells to further investigate its effects on cell viability and migration. The key pathways associated with ADAM17 were identified by gene set enrichment analysis (GSEA). It was found that ADAM9 and ADAM17 were significantly upregulated in gastric cancer and positive metastatic lymph node tissues. Further, there was a strong correlation between the survival times of patients and ADAM17 expression. ADAM17 was upregulated in gastric cancer cells with high metastatic potential. The viability of BGC-823 cells significantly increased following ADAM17 overexpression, whereas the viability and migration of SGC-7901 cells decreased following ADAM17 suppression. GSEA and western blot analysis revealed a positive correlation between the Notch and Wnt signaling pathways with ADAM17 expression. In conclusion, the increased expression of ADAM17 promoted the progression of gastric cancer, potentially via Notch and/or Wnt signaling pathway activation, and ADAM17 may serve as a useful prognostic marker.