Proj. 3 - Proteomic Response of Epithelial Cell Interactions with HIV

项目。

• 批准号: 8254424
• 负责人: THOMAS S MCCORMICK
• 金额: $ 31.32万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8254424
• 关键词: Address; Adhesions; African American; Anatomic Sites; Anatomy; Anti-Retroviral Agents; Apoptosis; Benchmarking; Binding; Biological Process; CXCR4 gene; Cell Communication; Cell Death; Cell Proliferation; Cells; Chemotaxis; Chronic; Clinical; Coculture Techniques; Communities; Complication; Cytoplasmic Tail; Data; Defensins; Dendritic Cells; Environment; Epidemiology; Epithelial; Epithelial Cells; Epithelium; Event; Exhibits; Exposure to; Female; Future; Genital system; Growth; HIV; HIV Infections; HIV Seropositivity; HIV-1; Heterosexuals; Highly Active Antiretroviral Therapy; Human; Human Papillomavirus; Immature Monocyte; Immune; Immune response; Immunocompromised Host; Immunologic Deficiency Syndromes; In Vitro; Individual; Infection; Inflammatory; Intervention; Leukocyte L1 Antigen Complex; Lichen Planus; Ligands; Location; Messenger RNA; Molecular Profiling; Mucosal Immunity; Mucous Membrane; Mutation; Normal tissue morphology; Nucleosides; Oral; Oral Manifestations; Oral candidiasis; Oral cavity; Oral mucous membrane structure; Oropharyngeal; Patients; Phenotype; Phosphorylation; Play; Population; Predisposition; Production; Property; Protease Inhibitor; Protein Analysis; Proteins; Proteome; Proteomics; Psoriasis; Recruitment Activity; Reverse Transcriptase Inhibitors; Risk; Role; Route; SLPI gene; Sampling; Signal Transduction; Site; Skin; Spottings; Stromal Cell-Derived Factor 1; Syndrome; Testing; Therapeutic; Tissues; Translating; Undifferentiated; Vagina; Viral; Vulnerable Populations; Wound Healing; acronyms; antimicrobial peptide; arrestin3; base; beta-Defensins; beta-defensin 3; beta-defensin-2; chemokine; cohort; cytokine; desensitization; insight; interest; keratinocyte; male; monocyte; oral cavity epithelium; oral wart; protein expression; protein profiling; receptor internalization; rectal; research study; response; steroid hormone; transmission process

We have previously demonstrated that oral epithelia produces human beta defensin-2 and-3 (hBD2, 3), innate immune molecules ordinarily inducible under inflammatory conditions for most epithelia, at higher endogenous levels in oral epithelia. Using 2D-DIGE assessment of human oral epithelial cells from HIV+ and HIV- individuals from vulnerable populations (mainly African Americans), we identified 153 proteins of interest; 137 (-90%) were down-regulated and 16 were up-regulated in samples obtained from HIV positive individuals versus control. Interestingly, in terms of their biological functions and significance, protein profiles consistent with cell death (apoptosis) were the most numerous followed by cell proliferation proteins as well as immunological response proteins, suggesting that both cellular and innate immune mechanisms may be altered as a result of HIV infection. Understanding the role that the epithelium plays in HIV infection and inherent differential susceptibility properties of epithelial tissues derived from various anatomic locations is of interest. We propose to (I) compare proteomic profiles of human oral epithelial cells (HOECs), female genital track epithelial cells (FGTECs) and skin-derived epithelial cells (SDECs) from HIV+ and HIV- subjects and to examine protein profiles in these epithelia following in vitro challenge with HIV or HAART therapy; (II) Compare innate and cellular immune response molecules among HOECs, FGTECs and SDECs at baseline and following challenge with HIV and HAART treatment as well as among epithelial cells obtained from wart (oral and vaginal) tissue; (III) Determine if proteomic response from HOECs, FGTECs or SDECs are altered by co-incubation with immune-derived undifferentiated and/or differentiated cells following exposure to human beta defensins. We hypothesize that beta defensins, and other antimicrobial peptides are elevated in tissue undergoing growth and high proliferation rates and that elevated levels of innate immune molecules could result in less viral transmission through the mucosal barrier. Additionally, oral complications of HIV infection may be altered by HIV therapeutics such as HAART or differences in endogenous levels of antimicrobial peptides. By studying protein profiles in the genital epithelia, a site extremely susceptible to HIV trancytosis and infection, and comparing them to oral and skin mucosa, new insights will be gained which could then be translated in the future into promoting protection in vulnerable mucosal barriers.

我们以前已经证明口腔上皮产生人β -防御素-2和3