Electrophilic PPARγ Ligands Attenuate IL-1β and Silica-Induced Inflammatory Mediator Production in Human Lung Fibroblasts via a PPARγ-Independent Mechanism.

Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ) ligands are small molecules that induce anti-inflammatory responses in a variety of tissues.

Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells.

Lambda phage vectors mediate gene transfer in cultured mammalian cells and in live mice, and in vivo phage-mediated gene expression is increased when mice are pre-immunized with bacteriophage lambda. We now show that, like eukaryotic viruses, bacteriophage vectors are subject to Fc receptor-mediated, antibody-dependent enhancement of infection in mammalian cells. Antibody-dependent enhancement of phage gene transfer required FcgammaRI, but not its associated gamma-chain, and was not supported by other FcgammaR family members (FcgammaRIIA, FcgammaRIIB, and FcgammaRIII).

Enhanced transduction of dendritic cells by FcgammaRI-targeted adenovirus vectors.

Background: The high affinity Fcgamma receptor I (FcgammaRI; aka CD64) is expressed by dendritic cells (DC) and antigens targeted to this receptor elicit enhanced immune responses. This study was designed to test the hypothesis that targeting an adenoviral (Ad) vector to FcgammaRI would lead to enhanced transduction of DC and an improved immune response to vector-encoded antigens.

Methods: A bispecific adaptor molecule consisting of a trimeric adenovirus fiber-binding moiety fused to a single-chain antibody specific for human FcgammaRI was generated.

A tractable method for simultaneous modifications to the head and tail of bacteriophage lambda and its application to enhancing phage-mediated gene delivery.

There is considerable interest in the use of bacteriophage vectors for mammalian cell gene transfer applications, due to their stability, excellent safety profile and inexpensive mass production. However, to date, phage vectors have been plagued by mediocre performance as gene transfer agents. This may reflect the complexity of the viral infection process in mammalian cells and the need to refine each step of this process in order to arrive at an optimal, phage-based gene transfer system.

Recombinant adenovirus type 5 vectors that target DC-SIGN, ChemR23 and alpha(v)beta3 integrin efficiently transduce human dendritic cells and enhance presentation of vectored antigens.

Recombinant adenoviruses (rAds) represent a promising system for vaccine delivery but transduce dendritic cells (DC) relatively poorly. To address this concern, we used a biotin-avidin linkage to conjugate rAd vectors to ligands which bind with high affinity to selected receptors on DC (ChemR23, alpha(v)beta3 integrin, and DC-SIGN). The targeted vectors had an enhanced ability to transduce human monocyte-derived DC compared to untargeted virus.

Valproic acid enhances gene expression from viral gene transfer vectors.

Viral vectors represent an efficient delivery method for in vitro and in vivo gene transfer, and their utility may be further enhanced through the use of pharmacologic agents that increase gene expression. Here, we demonstrate that valproic acid (VPA), a drug which is widely used for the treatment of epilepsy and mood disorders, enhances and prolongs expression of exogenous genes in cells transduced with various gene transfer agents, including adenovirus, adeno-associated virus and herpesvirus vectors. This effect occurs in a wide range of cell types, including both primary cells and cell lines, and appears to be associated with VPA's ability to function as a histone deacetylase inhibitor (HDACi).

Murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes.

Dendritic cells (DC) are potent antigen-presenting cells that play a crucial role in antigen-specific immune responses. Thus, the targeting of exogenous antigens to DC has become a popular approach for cancer immunotherapy and vaccine development. In this report, we studied the interplay between murine cytomegalovirus (MCMV) and human monocyte-derived DC.