Role of Integrin Expression in Adenovirus-Mediated Gene Delivery to the Intestinal Epithelium

Overview summary Previous studies of adenovirus-mediated gene transfer of the interleukin-1 receptor antagonist protein to rat jejunum have produced limited gene expression. In the present study, we have shown that integrins play a significant role in efficient adenoviral infection of the intestinal epithelium. As enterocytes differentiate, integrin expression decreases. This coincides with significant reduction in adenoviral transduction efficiency. Results from two in vitro models of the intestinal epithelium (Caco-2 and IEC-18 cells) show that αvβ3 integrins have the most influence on adenoviral internalization. Results from screening of rat intestinal segments for expression of the αvβ5 integrin suggest that, based on integrin expression, the ileum is a prime target for efficient adenovirus-mediated gene transfer. We have also found that administration of immunomodulating agents and inflammatory disease states provide a favorable environment for efficient internalization of adenoviral vectors due to up-regulation of integrin receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63160/1/hum.1998.9.4-561.pd

Inhibition of Interleukin-1-Induced Effects in Synoviocytes Transduced with the Human IL-1 Receptor Antagonist cDNA Using an Adenoviral Vector

Overview summary Adenovirus-mediated gene transfer into the cells of the synovial membrane may provide a means to deliver therapeutically active proteins for the local modification of the immune response in inflammatory arthropathies. In this study, we infected type B human synoviocytes in vitro and rabbit synovial lining membrane in vivo with a recombinant human adenovirus containing the cDNA for the human interleukin-1 receptor antagonist protein (IL-1ra). Expression of human IL-1ra was observed both in the transduced synoviocytes in vitro and in the microenvironment of the transduced rabbit synovial membrane in vivo, and the functional activity of the transgenic IL-1ra was suggested by in vitro inhibition of interleukin-1 (IL-1)-induced prostaglandin E2 (PGE2) production and by in vivo inhibition of IL-1-induced glycosaminoglycan (GAG) degradation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63124/1/hum.1995.6.3-307.pd

Pulmonary Inflammation Induced by Incomplete or Inactivated Adenoviral Particles

Overview summary The amount of pulmonary inflammation induced in mice by intratracheal administration of high doses of adenoviral vectors was compared to that induced by viral particles that lack the ability to express the genes that they contain. The number of inflammatory cells infiltrating the lung 6 days after particle administration was similar between animals receiving normal versus defective adenoviral particles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63169/1/hum.1995.6.12-1553.pd