Urokinase plasminogen activator surface receptor restricts HIV-1 replication by blocking virion release from the cell membrane.

The urokinase-type plasminogen activator (uPA) system consists of the proteinase uPA, its receptor (PLAUR/uPAR). Under physiological conditions, uPA and PLAUR are predominantly expressed by blood cells, including neutrophils, monocytes, and macrophages, and play important roles in cell activation, adhesion, migration, and extravasation. Here, we report that PLAUR, which is highly expressed in macrophages and dendritic cells (DCs) but hardly expressed in CD4+ T cells, inhibits the release of HIV-1 progeny virions from the cell membrane. Silencing PLAUR markedly enhanced the transmission of HIV-1 in macrophages and DCs. We further demonstrated that PLAUR is localized at the cell membrane to block the release of HIV-1 virions. Interestingly, we found that uPA compromises the PLAUR-mediated inhibition to slightly enhance HIV-1 production in primary macrophages and DCs. In the absence of PLAUR, this enhanced effect induced by uPA is abrogated. In conclusion, PLAUR is a new anti-HIV-1 protein produced in both macrophages and DCs where it inhibits HIV-1 transmission. This discovery may provide a novel therapeutic target for combating HIV.

Glyburide attenuates ozone-induced pulmonary inflammation and injury by blocking the NLRP3 inflammasome.

Glyburide is a classic antidiabetic drug that is dominant in inflammation regulation, but its specific role in ozone-induced lung inflammation and injury remains unclear. In order to investigate whether glyburide prevents ozone-induced pulmonary inflammation and its mechanism, C57BL/6 mice were intratracheally pre-instilled with glyburide or the vehicle 1 hour before ozone (1 ppm, 3 hours) or filtered air exposure. After 24 hours, the total inflammatory cells and total protein in bronchoalveolar lavage fluid (BALF) were detected. The pathological alternations in lung tissues were evaluated by HE staining. The expression of NLRP3, interleukin-1ß (IL-1ß), and IL-18 protein in lung tissues was detected by immunohistochemistry. Western blotting was used to examine the levels of caspase-1 p10 and active IL-1ß protein. Levels of IL-1ß and IL-18 in BALF were measured using ELISA kits. Glyburide treatment decreased the total cells in BALF, the inflammatory score, and the mean linear intercept induced by ozone in lung tissues. In addition, glyburide inhibited the expression of NLRP3, IL-18, and IL-1ß protein in lung tissues, and also suppressed NLRP3 inflammasome activation, including caspase-1 p10, active IL-1ß protein in lung tissues, IL-1ß, and IL-18 in BALF. These results demonstrate that glyburide effectively attenuates ozone-induced pulmonary inflammation and injury via blocking the NLRP3 inflammasome.