%0 Journal Article
%T Evaluation of signal transduction pathways after transient cutaneous adenoviral gene delivery
%A Lars Steinstraesser
%A Michael Sorkin
%A Frank Jacobsen
%A Sammy Al-Benna
%A Marco Kesting
%A Andreas Niederbichler
%A Jan-Michel Otte
%A Tobias Hirsch
%A Jadwiga Stupka
%A Hans-Ulrich Steinau
%A Matthias Schulte
%J BMC Immunology
%D 2011
%I BioMed Central
%R 10.1186/1471-2172-12-8
%X In vitro, keratinocytes were transfected with DNA, in the presence and absence of inhibitors for signalling molecules. In vivo, immunocompetent and athymic mice (n = 3 per group) were twice transduced with an Ad-vector.The results show an acute induction of type-I-interferon after in vitro transfection. Inhibition of PI3K, p38 MAPK, JNK and NFkappaB resulted in a decreased expression of type-I-interferon. In contrast to immunocompetent mice, athymic mice demonstrated a constant transgene expression and reduced inflammatory response in vivo.The results suggest an induction of the innate immunity triggered by cytoplasm localised DNA which is mediated by PI3K-, p38 MAPK-, JNK-, NFkappaB-, JAK/STAT- and ERK1/2-dependent pathways. A stable transgene expression and a reduced inflammatory response in immunodeficient mice have been observed. These results provide potential for an effective adenoviral gene delivery into immunosupressed skin.The skin is the largest organ of the body, accounting for about fifteen percent of our body weight, and covering the entire external surface. While many believe its role is merely as an external covering, the functions of the skin are far more complex. The skin consists of three main layers - the epidermis, the dermis, and the hypodermis, each with their own function. It is the epidermis, which creates a barrier to and protects from pathogens of the outside world. This highly specialised layer is mainly composed of keratinocytes, melanocytes and dendritic cells. Its accessibility and specific anatomical and biological properties make the skin a very interesting organ for in vivo and ex vivo gene therapy approaches. In case of cutaneous gene therapy, gene delivery can be easily controlled and the skin surgically excised if any side effects occur[1-3].Keratinocytes, the predominant epidermal cell type, are responsible for establishing a physical barrier and guaranteeing the structural integrity of the epidermis[3]. As the epidermis is known
%U http://www.biomedcentral.com/1471-2172/12/8