Translocation of microbes and changes of immunocytes in the gut of rapid- and slow-progressor Chinese rhesus macaques infected with SIVmac239.

Human/simian immunodeficiency virus (HIV/SIV) infection can cause severe depletion of CD4(+) T cells in both plasma and mucosa; it also results in damage to the gut mucosa barrier, which makes the condition more conducive to microbial translocation. In this study, we used SIV-infected Chinese rhesus macaques to quantify the extent of microbial translocation and the function of immune cells in the entire gastrointestinal tract and to compare their differences between rapid and slow progressors. The results showed that in the slow progressors, microbial products translocated considerably and deeply into the lamina propria of the gut; the tissue macrophages had no significant differences compared with the rapid progressors, but there was a slightly higher percentage of mucosal CD8(+) T cells and a large amount of extracellular microbial products in the lamina propria of the intestinal mucosa of the slow progressors. The data suggested that although microbial translocation increased markedly, the mucosal macrophages and CD8(+) T cells were insufficient to clear the infiltrated microbes in the slow progressors. Also, therapies aimed at suppressing the translocation of microbial products in the mucosa could help to delay the progression of SIV disease.

Spherical silica nanoparticles promote malignant transformation of BEAS-2B cells by stromal cell-derived factor-1α (SDF-1α).

OBJECTIVE: This study aimed to examine the role of spherical silica nanoparticles (SiNPs) on human bronchial epithelial (BEAS-2B) cells through inflammation. METHODS: Human mononuclear (THP-1) cells and BEAS-2B cells were co-cultured in transwell chambers and treated with 800 mmol/L benzo[ a]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and 12.5 µg/mL SiNPs for 24 hours. For controls, cells were treated with BPDE alone. Subcutaneous tumorigenicity and epithelial-mesenchymal transition (EMT) of BEAS-2B cells were measured. The cells were blocked with a stromal cell-derived factor-1α (SDF-1α)-specific antibody. EMT was analyzed in cells treated with 800 mmol/L BPDE and 12.5 µg/mL SiNPs relative to matched control cells and xenografts in vivo. Serum SDF-1α levels were measured in 23 patients with lung adenocarcinoma in Xuanwei, in 25 with lung adenocarcinoma outside Xuanwei, and in 22 with benign pulmonary lesions in Xuanwei. RESULTS: SiNPs significantly promoted tumorigenesis and EMT, induced the release of SDF-1α, and activated AKT (ser473) in BEAS-2B cells. EMT and phosphorylated AKT (ser473) and glycogen synthase kinase-3ß levels were decreased when blocked by SDF-1α antibody in BEAS-2B cells. SDF-1α was mainly secreted by THP-1 cells. CONCLUSION: SiNPs combined with BPDE promote EMT of BEAS-2B cells via the AKT pathway by inducing release of SDF-1α from THP-1 cells.