ABSTRACT
BACKGROUND: Psoriasis is a chronic and relapsing inflammatory skin disease associated with various immunologic abnormalities. Repeated subcutaneous injection of interleukin-4 (IL-4) has been established as an effective treatment to counteract psoriasis. OBJECTIVE: We investigated whether gene therapy using IL-4 expression plasmid (pIL-4) via transdermal delivery was an alternative treatment for psoriasis. In our experiment, dimethylsulfoxide (DMSO) was used as a penetration enhancer. METHODS: At first, the penetration efficiency of the complex of reporter plasmid accompanied by DMSO was investigated both in vitro and in vivo. Then, the antipsoriasis efficiency of the treatment with pIL-4-DMSO was tested in mice. RESULTS: The expression of the reporter gene was detected in epidermis and dermis both in vitro and in vivo. More importantly, the psoriasis symptoms were relieved, and significant reductions in some psoriasis-associated factors were observed after pIL-4-DMSO treatment. CONCLUSION: We conclude that the topical application of pIL-4-DMSO can treat psoriasis to a significant extent.
Subject(s)
Genetic Therapy/methods , Interleukin-4/genetics , Psoriasis/therapy , Transduction, Genetic/methods , Administration, Cutaneous , Animals , Dimethyl Sulfoxide/chemistry , Female , Mice , Mice, Transgenic , Plasmids , Psoriasis/pathologyABSTRACT
Vesicular stomatitis virus (VSV) matrix (M) protein can directly induce apoptosis by inhibiting host gene expression when it is expressed in the absence of other viral components. Previously, we found that the M protein gene complexed to DOTAP-cholesterol liposome (Lip-MP) can suppress malignant tumor growth in vitro and in vivo; however, little is known regarding the biological effect of Lip-MP combined with radiation. The present study was designed to determine whether Lip-MP could enhance the antitumor activity of radiation. LLC cells treated with a combination of Lip-MP and radiation displayed apparently increased apoptosis compared with those treated with Lip-MP or radiation alone. Mice bearing LLC or Meth A tumors were treated with intratumoral or intravenous injections of Lip-MP and radiation. The combined treatment significantly reduced mean tumor volumes compared with either treatment alone in both tumor models and prolonged the survival time in Meth A tumor models and the intravenous injection group of LLC tumor models. Moreover, the antitumor effects of Lip-MP combined with radiation were greater than their additive effects when compared with the expected effects of the combined treatment in vivo. This study suggests that Lip-MP enhanced the antitumor activity of radiation by increasing the induction of apoptosis.
Subject(s)
Apoptosis/radiation effects , Gamma Rays , Genetic Therapy , Neoplasms/genetics , Neoplasms/radiotherapy , Viral Matrix Proteins/genetics , Viral Matrix Proteins/therapeutic use , Animals , Cell Line, Tumor , Cell Proliferation , Fatty Acids, Monounsaturated/metabolism , Liposomes/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasms/pathology , Quaternary Ammonium Compounds/metabolism , Tumor Stem Cell AssayABSTRACT
FAM92A1 (named FAM92A1-271) belongs to the family of proteins with conserved DUF1208 domains. Its function remains elusive. We identified two novel transcript variants (FAM92A1-251, FAM92A1-289) of FAM92A1. The presence of these transcripts in cancerous and normal cells, as well as their influence on cell proliferation and apoptosis, were investigated. The subcellular location of FAM92A1 was determined by fluorescence microscopy. We found that FAM92A1-271 and FAM92A1- 289 were highly expressed in both normal and cancerous cells, but FAM92A1-251 was only expressed at a moderate level in both types of cell. Overexpression of FAM92A1-271, FAM92A1-251 and FAM92A1-289 inhibited cell proliferation, caused S-phase arrest and induced apoptosis. Subcellular localization showed that FAM92A1 localizes to the nucleus. Our results show that FAM92A1 has different splicing variants, and that it may take part in regulating cell proliferation and apoptosis.
Subject(s)
Proteins/genetics , Alternative Splicing , Amino Acid Sequence , Apoptosis/genetics , Cell Cycle/genetics , Cell Proliferation , Genes, Neoplasm , HeLa Cells , Humans , Molecular Sequence Data , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Structure, Tertiary/genetics , Proteins/metabolism , Sequence Homology, Amino Acid , Tissue Distribution , Transfection , Tumor Cells, CulturedABSTRACT
We have identified a novel Xenopus gene (xVAP019) encoding a DUF1208 domain containing protein. Using whole-mount in situ hybridization and RT-PCR, we found abundant xVAP019 maternal transcripts in the animal hemisphere during the cleavage stages and blastula stages. During gastrulation xVAP019 is differentially expressed with higher levels in the animal helf and the highest in marginal zone, then further expressed widely at neuronal stages with strongest signals in the prospective CNS regions and the epidermal ectoderm. Subsequently xVAP019 was expressed predominantly in the head, the eyes, the otic vesicle, branchial arches, spinal cord, notochord, somites, and tailbud. It is absent or very weak in the endoderm. Injecting a morpholino oligo complementary to xVAP019 mRNA or injecting a caped xVAP019 mRNA caused most of embryos to die during gastrulation and neurulation. Overexpression of xVAP019 mRNA also led to eye defect, shorten interocular distance, small body size and abnormal pigment formation in parts of the survival embryos. Similar effects were induced by injecting the xVAP019 human homologous gene FAM92A1. Our results suggest that xVAP019 is essential for the normal ectoderm and axis mesoderm differentiation and embryos survival. This investigation is for the first time in vivo study examining the role of this novel gene and reveals an important role of xVAP019 in embryonic development.
