Many human skin diseases display a hyperproliferative or proliferative epidermis, or cutaneous inflammation, or combinations of these two pathological characteristics. As an example, the keratinocytes of the psoriatic epidermis are both hyperproliferative and produce elevated levels of the Amphiregulin EGF-like growth factor, and the IL-8, ILalpha and TNF-alpha cytokines, which could both attract and activate inflammatory cells, and promote psoriatic epidermal keratinocyte hyperproliferation. Additionally, the aberrant activity of the immune system may direct the mitogenic activation of these cells by activating the endogenous epidermal growth factor (EGF) pathway in the psoriatic epidermal keratinocytes. Our proposed investigation will examine activity of charged polymeric compounds that may block the EGF pathway in human keratinocyte cultures and penetrate into reconstructed human epidermis the results of the proposed study will determine whether these charged compounds might represent new non-steroidal drugs for further testing as therapeutics for inflammatory-proliferative human skin disease such as psoriasis and dermatitis.
Public Health Relevance: This proposal is designed to synthesize and test new drugs for the treatment of the commonly observed human inflammatory-proliferative skin diseases such as psoriasis and dermatitis. It is hoped that the results of this study will produce new, safe and effective topical therapies for individuals suffering from these common skin diseases.
Thesaurus Terms: 3-10c; Amcf-I; Adrenal Cortex Hormones; Amphiregulin; Animal Growth Regulators, Transforming Growth Factors; Anthelone U; Anti-Sense Oligonucleotides; Antibodies; Antirejection Therapy; Antisense Agent; Antisense Oligonucleotides; Arginine-Serpin; Arthritis, Psoriatic; Autocrine Systems; Binding; Binding (Molecular Function); Crgf; Cxcl8; Cachectin; Cachectin-Tumor Necrosis Factor; Cell Communication And Signaling; Cell Signaling; Cells; Cellulose; Characteristics; Charge; Colorectum Cell-Derived Growth Factor; Corticoids; Corticosteroids; Cutaneous; Cutaneous Disorder; Cycloamylose; Cyclodextrins; Cyclomaltooligosaccharides; Dermal; Dermatitis; Dermatoses; Dextran Sulfate; Dextran, Hydrogen Sulfate; Dextrans; Dextrins; Drug Administration, Topical; Drugs; Egf; Egfr; Erbb Protein; Erbb1; Environment; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Kinase; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase; Epidermal Growth Factor-Urogastrone; Epidermis; Family; Family Member; Feedback; Gcp-1; Gcp1; Gfac; Gene Expression Inhibitor; Growth Agents; Growth Factor; Growth Factor Receptors; Growth Factors, Proteins; Growth Substances; Her1; Heparin; Heparin Binding; Heparinic Acid; Heparinoids; Histologic; Histologically; Histopathology; Human; Human Urinary Gastric Inhibitor; Human, General; Hydrogen Oxide; Igf-1; Igf-I; Igf-I-Smc; Igf1; Il-8; Il8; Il8 Gene; Inflm; Immune System; Immunosuppressive Therapy; Individual; Inflammation; Inflammatory; Injection Of Therapeutic Agent; Injections; Inorganic Sulfates; Insulin-Like Growth Factor 1; Insulin-Like Growth Factor I; Insulin-Like Somatomedin Peptide I; Intracellular Communication And Signaling; Investigation; Investigators; K60; Keratinocyte-Derived Autocrine Factor; Knee Joint; Lect; Luct; Lynap; Lesion; Ligands; Liposomal; Liposomes; Mdncf; Monap; Mammals, Mice; Man (Taxonomy); Man, Modern; Medication; Mice; Molecular Interaction; Monocyte Arg-Serpin; Murine; Mus; Naf; Oligo; Oligonucleotides; Oligonucleotides, Antisense; Pai-2; Planh2; Pathology; Pathway Interactions; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Physiologic; Physiological; Plasminogen Activator Inhibitor 2; Plasminogen Activator Inhibitor Type Ii; Polyanhydroglucuronic Acid; Proteins; Proto-Oncogene, Growth Factor Receptor; Psoriasis; Psoriasis Arthropathica; Psoriasis, Arthritic; Psoriatic Arthritis; Publishing; Receptor, Egf; Receptor, Tgf-Alpha; Receptor, Urogastrone; Receptors, Epidermal Growth Factor-Urogastrone; Relative; Relative (Related Person); Reporting; Research Personnel; Researchers; Sbir; Sbirs (R43/44); Scid; Scid Mice; Scyb8; Schwannoma-Derived Growth Factor; Serine Or Cysteine Proteinase Inhibitor Clade B Member 2; Severe Combined Immunodeficient Mice; Signal Transduction; Signal Transduction Systems; Signaling; Skin; Skin Diseases; Skin Diseases And Manifestations; Small Business Innovation Research; Small Business Innovation Research Grant; Somatomedin C; Starch; Sulfates; Sulfates, Inorganic; Sulfates, Unspecified Or Sulfate Ion; Synovitis; System; System, Loinc Axis 4; Tnf; Tnf Alpha; Tnf Protein, Human; Tnf Superfamily, Member 2 Protein, Human; Tnf-2 Protein, Human; Tnf-Alpha; Tnfa; Tnfsf2 Protein, Human; Tsg-1; Testing; Therapeutic; Therapeutic Corticosteroid; Therapeutic Immunosuppression; Therapy, Anti-Rejection; Topical Application; Toxic Effect; Toxicities; Transforming Growth Factor Alpha Receptor; Transforming Growth Factors; Transgenic Mice; Tumor Growth Factors; Tumor Necrosis Factor; Tumor Necrosis Factor-Alpha; Tumor Necrosis Factor-Alpha (Macrophage-Derived); Type 2 Plasminogen Activator Inhibitor; Unspecified Or Sulfate Ion Sulfates; Urogastrone; Water; Alpha Heparin; Alpha-Cellulose; Aqueous; Artificial Immunosuppression; Autocrine; B-Enap; Beta-Urogastrone; Biological Signal Transduction; Body System, Allergic/Immunologic; C-Erbb-1; C-Erbb-1 Protein; Caloreen; Cellulose Sulfate; Cellulose, Hydrogen Sulfate; Colorectal Cell-Derived Growth Factor; Colorectal-Associated Growth Factor; Colorectum-Associated Growth Factor; Cytokine; Design; Designing; Dextran; Dextrin; Drug/Agent; Early Onset; Erbb-1; Erbb-1 Proto-Oncogene Protein; Erbbl; Gene Product; Human Tnf Protein; Immunosuppression; Inhibitor; Inhibitor/Antagonist; Interest; Keratinocyte; Keratinocyte Autocrine Factor; Molecular Mass; Neutralizing Mab; Neutralizing Monoclonal Antibodies; Organ System, Allergic/Immunologic; Pathway; Proto-Oncogene Protein C-Erbb-1; Psoriasiform; Psoriatic; Psoriatiform; Public Health Relevance; Severe Combined Immune Deficiency; Skin Disorder; Sulfate; Topical Administration; Topical Drug Application; Topically Applied; Tumor Necrosis Factor, Human; Tumor Necrosis Factor-2 Protein, Human; Tumor Necrosis Factor-Alpha Promoter Allele-2 Protein, Human
