Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases (STDs) in the USA, and therefore, of major public health significance. C. trachomatis invades the mucosal surface of the female genital tract consequently triggering secretion of inflammatory mediators, which are thought to play significant roles in its pathogenesis. Prolonged exaggerated production of pro-inflammatory cytokines at the female genital track causes damage to the fallopian tube often leading to infertility and ectopic pregnancy. On the other hand, anti-inflammatory cytokines control the production levels of pro-inflammatory cytokines thus reducing these clinical manifestations. Therefore, coordinating the production and activities of cytokines is crucial to reducing inflammation. Tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-12 are the most important pro-inflammatory mediators in the female genital tract infection of C. trachomatis. They are secreted by macrophages in the early phase of infection and are responsible for triggering several classical features of inflammation. With the advent of nanobiotechnology, surface coated pure metal such as silver-polyvinyl pyrrolidone nanoparticles (Ag-PVP) can now be made into nanometer-sized particles. Previously we demonstrated the ability of Ag-PVP nanoparticles to inhibit respiratory syncytial virus (RSV) by 44% (Sun et al., 2008). Given that Ag-PVP also has anti-inflammatory properties we sought to investigate Ag-PVP’s role in reducing inflammatory responses in a C. trachomatis in vitro infection model. We hypothesized that Ag-PVP will down-regulate the production of pro-inflammatory cytokines in C. trachomatis-infected epithelial (HeLa) cells and J774 macrophages, and may serve to control inflammation during the initial phase of the disease. To test our hypothesis, we exposed J774 and HeLa cells infected with C. trachomatis to various concentrations of Ag-PVP (2.5, 1.25, 0.63, 0.31 and 0.16 g/mL) to assess its anti-inflammatory effect on the production of pro-inflammatory cytokines. Our results, as demonstrated using cytokine ELISA, confocal microscopy, and MTT assay, indicate that Ag-PVP at 2.5 µg/mL significantly (P < 0.05) abrogated the production levels of TNF, IL-6 and IL-8 in a dose-dependent fashion. Similar down-modulation of inflammatory mediators in cells were observed when C. trachomatis recombinant major outer membrane protein (rMOMP) was used as a stimulant. The MTT assay revealed that the anti-inflammatory effect of Ag-PVP at 2.5 g/mL was not due to death of inflammatory cells. These findings provide evidence for, and contribute, to the understanding of the anti-inflammatory properties of Ag-PVP, and may also give a novel therapeutic direction for controlling inflammation during C. trachomatis infection of the female genital tract.
Journal: TechConnect Briefs
Volume: 3, Nanotechnology 2011: Bio Sensors, Instruments, Medical, Environment and Energy
Published: June 13, 2011
Pages: 447 - 450
Industry sector: Medical & Biotech