development-an-economical-dna-delivery-system-acufection-its

Development of an Economical DNA Delivery System by "Acufection" and its Application to Skin Research

Dysregulation of immune response in skin is associated with numerous human skin disorders. Direct transfer of immune-related genes into skin tissue is a ...

National Taiwan University College of Medicine

In a routine phenotype-driven screen, we identified a point mutation in exon 7 of the IL-15 gene in Pedigree 191 (deficient memory (DM)) of N-ethyl-N-nitrosourea mutagenized mice. The DM epidermis expressed an alternatively spliced IL-15 mRNA isoform, IL-15ΔE7, and a wild-type (WT) IL-15 isoform at comparable levels. Mechanical stimulation of DM skin or DM skin graft transplanted onto the WT host resulted in reduced keratinocyte activation and inhibition of neutrophil infiltration into the dermis, demonstrating that DM keratinocytes produced less inflammatory response to external stimulation. Ectopic expression of IL-15ΔE7 in WT skin prevented abrasion-induced epidermal thickening, blocked the accumulation of nuclear antigen Ki67(+) cells in the basal and the suprabasal cell layers, increased loricrin expression, and also increased keratinocyte CXCL1 and G-CSF production. IL-15ΔE7 also profoundly blocked neutrophil infiltration in SDS- or immiquimod (IMQ)-treated WT skin. Recombinant IL-15ΔE7 failed to activate STAT-5 and its downstream target bcl-2 expression. Our study points to IL-15ΔE7 as a potential therapeutic agent for treating neutrophilia-associated inflammatory skin disorders.

An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation.

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The immediate-early protein, IE62 is the predominant VZ virion tegument protein, transactivating the expression of all kinetic classes of VZV genes. IE62 is localized to punctae that form DNA replication compartments in the nuclei of VZV infected cells. The morphological changes and the increase in the size of replication compartments that express IE62 are correlated with production of VZ virions. Mammalian Mediator serves as a coactivator of IE62 and functions by bridging DNA-binding transcription factors¸ RNA polymerase II (RNAP II) and their target DNAs for VZV replication. While VZV is highly sensitive to type I interferons (IFNs), how IFN-α inhibits early events during VZV replication is poorly understood.

Type I interferon inhibits varicella-zoster virus replication by interfering with the dynamic interaction between mediator and IE62 within replication compartments.

Turnover of physicians might be responsible for reducing patients' trust and affecting hospital performance. This study aimed to understand physicians' psychological status regarding their hospital work environment and the resources of independent practitioners.

Article	Year
An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation. The Journal of investigative dermatology\| PubMed ID: 25615554	2015
Type I interferon inhibits varicella-zoster virus replication by interfering with the dynamic interaction between mediator and IE62 within replication compartments. Cell & bioscience\| PubMed ID: 26985360	2016
Facility evaluation of resigned hospital physicians:managerial implications for hospital physician manpower. BioMedicine\| PubMed ID: 27854049	2016

Tsung-Lin Lee

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