Morphine Actions on the Immune System

吗啡对免疫系统的作用

• 批准号: 7172637
• 负责人: SULIE L. CHANG
• 金额: $ 10.88万
• 依托单位: SETON HALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-05 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7172637
• 关键词: Adhesions; Adrenal Glands; Affect; Affinity; Anti-Inflammatory Agents; Anti-inflammatory; Area; Arts; Attenuated; Award; Bacterial Infections; Biological Assay; Blood Coagulation Factor; Blood capillaries; Brain; Canis familiaris; Cell Nucleus; Cell model; Cell physiology; Cells; Characteristics; Chemosensitization; Chronic; Condition; Corticosterone; Corticotropin-Releasing Hormone; Data; Detection; Disease; Disseminated Intravascular Coagulation; Drug abuse; Education; Endorphins; Endothelial Cells; Endotoxins; Equilibrium; Equipment; Exposure to; Fibrinopeptide A; Fluorescence; G-Protein-Coupled Receptors; GTP-Binding Proteins; Genetic Transcription; Goals; Grant; Hypothalamic structure; Immune; Immune response; Immune system; In Vitro; Independent Scientist Award; Infection; Inflammation; Inflammatory; Inflammatory Response; Interleukin-1; Interleukin-1 Receptors; Interleukin-1 beta; Interleukin-6; Interleukins; Kidney; Leukocytes; Ligand Binding; Lipopolysaccharides; MDCK cell; Mediating; Mentors; Mesentery; Messenger RNA; Methodology; Microarray Analysis; Molecular; Morphine; NF-kappa B; Neurons; Neurosecretory Systems; New Jersey; Opiates; Opioid; Opioid Peptide; Opioid Receptor; Pathway interactions; Pituitary Gland; Plasma; Polymerase Chain Reaction; Process; Production; Rattus; Reaction; Reader; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Shock; Signal Transduction Pathway; Students; System; Testing; Time; Training Programs; Transmembrane Domain; Tumor Necrosis Factor-alpha; Work; antithrombin III-protease complex; base; capillary; career; cytokine; design; drug of abuse; endogenous opioids; experience; hypothalamic-pituitary-adrenal axis; in vivo; mu opioid receptors; neuroimmunology; paraventricular nucleus; pressure; protein expression; receptor; receptor expression; response; venule

DESCRIPTION (provided by applicant): This application for a K02 Independent Scientist Award is submitted to enable me to devote additional time to my research projects and other research-related activities and to further my research career in the field of neuroimmunology of drug abuse. The primary goal of my research is to define the influence of drugs of abuse, such as morphine, on immune responses and their progression. We have previously reported that chronic exposure to morphine suppresses the hypothalamic-pituitary-adrenal (HPA) axis in vivo by desensitizing interleukin-1beta (IL-1beta)-induced neuronal activation of the hypothalamic paraventricular nucleus, an area of the brain involved in the activation of the HPA axis, thus, inhibiting IL-1beta-induced transcription of corticotropin releasing factor mRNA by the hypothalamus and decreasing the production of anti-inflammatory agents, such as corticosterone, by the adrenal gland. Conversely, we have found that morphine potentiates IL-1beta-induced immune responses, such as leukocyte-endothelial adhesion (LEA), in mesenteric venules. Thus, it appears that chronic morphine exposure can promote a potentially damaging inflammatory reaction by disrupting the balance between IL-1?-mediated local inflammatory responses, such as LEA, and the anti-inflammatory effects of the HPA axis. Recently, my R01 grant (DA07058-12) entitled, "Morphine actions on the immune system", was renewed for an additional five years (3/15/02-1/31/07), and I was also awarded an equipment grant by the New Jersey Commission on Higher Education to purchase a sequence detection system, a fluorescent imager, and a fluorescent plate reader. The studies in my R01 project are designed to extend our previous findings to define the mechanisms by which morphine influences the progression of bacterial infection. The Specific Aims are to define the molecular and cellular processes by which bacterial endotoxins modulate mu opioid receptor (MOR)-dependent pathways and how such modulation is related to the progression of endotoxin shock. This K02 award will enable me to devote maximum time to: 1) working on the aims of my research projects, 2) gaining experience in the use of state-of-the-art methodologies, including real time PCR, fluorescence-based biological assays, and microarray technology, 3) mentoring research students and junior researchers, and 4) establishing an ongoing formal training program in the responsible conduct of research for my lab staff and students.

描述（由申请人提供）：