Search

Background and objective E-cigarettes are often marketed and thought of as emitting harmless vapour; however, verification of their safety for non-smokers is scarce. We have previously shown that E-cigarettes cause decreased phagocytosis of bacteria by macrophages via reductions in surface bacterial recognition receptors. This study assessed the effect of E-cigarette constituents, 3 E-liquid apple flavours, nicotine, vegetable glycerine and propylene glycol, on bronchial epithelial cell viability, apoptosis and cytokine secretion and macrophage phagocytosis of apoptotic airway cells and phagocytic recognition molecules. Methods Cell necrosis and apoptosis were measured by Sytox Green stain and Annexin V. Efferocytosis was measured by internalization of pHrodo Green labelled apoptotic airway cells by macrophages. Expression of macrophage cell surface apoptotic cell receptors was measured by flow cytometry. Cytokine release by E-cigarette-exposed airway cells was measured by cytokine bead array. Results E-cigarette vapour increased primary bronchial epithelial necrosis and apoptosis. E-cigarette vapour reduced efferocytosis (lowest flavour 12.1%) versus control (20.2%, P = 0.032). The efferocytosis receptor CD44 was reduced by one flavour (MFI 1863 vs 2332 control, P = 0.016) and all components reduced expression of CD36, including the glycol bases (MFI 1067-12 274 vs 1415 control). Reduced secretion of TNF-α, IL-6, IP-10, MIP-1α and MIP-1β was observed for all flavour variants. Conclusion E-cigarettes can cause bronchial epithelial apoptosis and macrophage efferocytosis dysfunction via reduced expression of apoptotic cell recognition receptors. These data further show that E-cigarettes should not be considered harmless to non-smokers and their effects may go far beyond cytotoxicity to cells.

Ovarian cancer metastasis is characterized by the shedding of malignant cells from the surface of the ovary and their implantation onto the peritoneal surface, which lines the abdominal cavity. As the factors promoting this process are poorly understood, we investigated the ovarian cancer-peritoneal interaction by means of in vitro coculture experiments with ovarian cancer (OVCAR-5 and SKOV-3) and peritoneal (LP-9) cells. One of the proteins differentially expressed in the coculture secretome was identified by MALDI-TOF/TOF mass spectrometry as the extracellular matrix protein transforming growth factor-beta-induced protein (TGFBIp, also known as beta ig-H3). Immunohistochemistry showed high TGFBIp levels in normal surface ovarian epithelial and peritoneal cells, whereas TGFBIp levels in primary serous ovarian carcinomas and matching metastatic implants was very low. In functional in vitro experiments, treatment with recombinant TGFBIp significantly increased the motility and invasiveness of OVCAR-5 and SKOV-3 cells and significantly increased ovarian cancer cell (OVCAR-5, OVCAR-3 and SKOV-3) adhesion to LP-9 cells. TGFBIp was found to be processed at both the N-and C-terminus in the secretome of the ovarian cancer-peritoneal cell coculture. Plasmin inhibitors blocked TGFBIp processing and significantly reduced OVCAR-5 cell adhesion to peritoneal cells. We conclude that TGFBIp expressed by peritoneal cells increases the metastatic potential of ovarian cancer cells. TGFBIp is therefore a potential novel therapeutic target against ovarian cancer. Refereed/Peer-reviewed

E-cigarettes are perceived as harmless; however, evidence of their safety is lacking. New data suggests E-cigarettes discharge a range of compounds capable of physiological damage to users. We previously established that cigarette smoke caused defective alveolar macrophage phagocytosis. The present study compared the effect E-cigarette of components; E-liquid flavors, nicotine, vegetable glycerine, and propylene glycol on phagocytosis, proinflammatory cytokine secretion, and phagocytic recognition molecule expression using differentiated THP-1 macrophages. Similar to CSE, phagocytosis of NTHi bacteria was significantly decreased by E-liquid flavoring (11.65–15.75%) versus control (27.01%). Nicotine also decreased phagocytosis (15.26%). E-liquid, nicotine, and E-liquid+ nicotine reduced phagocytic recognition molecules; SR-A1 and TLR-2. IL-8 secretion increased with flavor and nicotine, while TNFα, IL-1β, IL-6, MIP-1α, MIP-1β, and MCP-1 decreased after exposure to most flavors and nicotine. PG, VG, or PG:VG mix also induced a decrease in MIP-1α and MIP-1β. We conclude that E-cigarettes can cause macrophage phagocytic dysfunction, expression of phagocytic recognition receptors and cytokine secretion pathways. As such, E-cigarettes should be treated with caution by users, especially those who are nonsmokers. Refereed/Peer-reviewed