Recombinant Protein Vaccines Formulated with Enantio-Specific Cationic Lipid R-DOTAP Induce Protective Cellular and Antibody-Mediated Immune Responses in Mice.

Adjuvants are essential components of subunit vaccines added to enhance immune responses to antigens through immunomodulation. Very few adjuvants have been approved for human use by regulatory agencies due to safety concerns. Current subunit vaccine adjuvants approved for human use are very effective in promoting humoral immune responses but are less effective at promoting T-cell immunity.

Bone marrow dendritic cell-mediated regulation of TLR and B cell receptor signaling in B cells.

Dendritic cells (DCs) play an essential role in regulation of immune responses. In the periphery, Ag presentation by DCs is critical for adaptive responses; for this reason, DCs are often targets of adjuvants that enhance vaccine responses. Activated mature DCs enhance B cell activation and differentiation by providing cytokines like BAFF and a proliferation-inducing ligand.

Effects of long-term pioglitazone treatment on peripheral and central markers of aging.

Background: Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPARgamma) and are used clinically to help restore peripheral insulin sensitivity in Type 2 diabetes (T2DM). Interestingly, long-term treatment of mouse models of Alzheimer's disease (AD) with TZDs also has been shown to reduce several well-established brain biomarkers of AD including inflammation, oxidative stress and Abeta accumulation. While TZD's actions in AD models help to elucidate the mechanisms underlying their potentially beneficial effects in AD patients, little is known about the functional consequences of TZDs in animal models of normal aging.

Inhibition of interleukin-10 signaling in lung dendritic cells by toll-like receptor 4 ligands.

The homeostatic microenvironment in lung is immunosuppressive and interleukin-10 (IL-10) helps maintain this microenvironment. Despite constitutive production of IL-10 in normal lung, macrophages (MØs) and dentritic cells (DCs) remain capable of responding to microorganisms, suggesting that these innate immune cells have a mechanism to override the immunosuppressive effects of IL-10. Prior studies by the authors revealed that Toll-like receptor (TLR) ligands inhibit IL-10 receptor signaling in alveolar macrophages (AMØs), thereby obviating the immunosuppressive activity of IL-10.

Inhibition of IL-10 receptor function in alveolar macrophages by Toll-like receptor agonists.

Despite an immunosuppressive lung environment, alveolar macrophages (AM) retain the capacity to respond to microorganisms. This report demonstrates that IL-10, constitutively produced by normal alveolar epithelium, stimulates signal transduction through the IL-10R on AM and that IL-10R function can be inhibited by stimulation of Toll-like receptor (TLR) on AM. IL-10 mRNA and protein were constitutively expressed in normal alveolar epithelium of mice, and IL-10R were constitutively expressed on normal murine AM.