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Study of gamma interferon agonists/mimetics

γ干扰素激动剂/模拟物的研究

基本信息

批准号：
7777372
负责人：
HOWARD M JOHNSON
金额：
$ 36.26万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-09-15 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7777372
关键词：
Address Agonist Agreement Antibodies Antiviral Agents Body Weight decreased Brain CD4 Positive T Lymphocytes Cells Communicable Diseases Coupled Cytokine Inducible SH2-Containing Protein Cytotoxic T-Lymphocytes Data Disclosure Dose Ectromelia Exhibits Florida Fluorescein-5-isothiocyanate Goals Helper-Inducer T-Lymphocyte Histocytochemistry IL4 gene Immune system In Vitro Infection Interferon Type II Interferons Interleukin-4 Kidney Liver Lung Macrophage Activation Malignant Neoplasms Measures Mediation Minor Monitor Mouse Pox Virus Mus Natural Immunity Natural Killer Cells Oral Oral Administration Palmitates Peptides Pharmaceutical Preparations Poxviridae Poxviridae Infections Property Proteins Public Health Publications Published Comment Reagent Relative (related person)Role Smallpox Spleen Stress T cell response TLR4 gene Testing Universities Vaccinia Vaccinia virus Viral Virus Virus Diseases Voice adaptive immunity cytokine expectation immune function intraperitoneal member mimetics novel novel therapeutics research study response small molecule success synergism

项目摘要

DESCRIPTION (provided by applicant): Gamma interferon (IFN3) is an essential cytokine for mediation of immune functions that are critical for surveillance against infections and cancer. Important aspects of innate immunity, adaptive immunity, macrophage activation, natural killer cell activity, helper T cell responses, as well as cytotoxic T cell responses are all critically modulated by IFN3. We have developed small peptide mimetics of IFN3. The IFN3 mimetics exhibit antiviral activity against a variety of viruses including amelioration of the lethal effects of the poxvirus vaccinia in mice under conditions where intact IFN3 is ineffective because of anti- IFN proteins produced by poxviruses. The activating effects of IFN3 are suppressed by proteins called suppressors of cytokine signaling (SOCS), of which SOCS-1 is an important member. We have developed a small molecule SOCS-1 antagonist. In this renewal, we propose to study the interaction between IFN3, IFN3 mimetics, and SOCS-1 antagonist as per AIMs below to positively regulate the IFN responses of cells of the immune system and enhancement of protection of mice against vaccinia and ectromelia viruses with a view toward an IFN and SOCS-1 antagonist drug against smallpox. We hypothesize that our small peptide IFN mimetics and SOSC-1 antagonist represent novel antivirals against lethal poxvirus infections. 1. Protection of mice against lethal vaccinia virus infections by IFN mimetics. Effect of SOCS-1 antagonist on protection. 2. Compare intraperitoneal versus oral administration of IFN mimetic peptides for their relative ability to protect mice against lethal vaccinia virus infection. Effect of SOCS-1 antagonist. 3. Protection of mice against lethal ectromelia virus infection by IFN mimetics and SOCS-1 antagonist. 4. Protection of mice against superlethal ectromelia virus encoding the interleukin-4 (IL-4) gene by IFN mimetics and SOCS-1 antagonist. 5. Determine immunological aspects of treatment of mice with IFN mimetics. Effect of SOCS-1 antagonist. PUBLIC HEALTH RELEVENCE: Our interferon mimetic is a novel therapeutic for treating viral and other infectious diseases. The SOCS-1 antagonist should provide a new paradigm to boosting the immune system against infections and cancer.

描述（由申请人提供）：γ 干扰素 (IFN3) 是调节免疫功能的重要细胞因子，对于监测感染和癌症至关重要。先天免疫、适应性免疫、巨噬细胞激活、自然杀伤细胞活性、辅助性 T 细胞反应以及细胞毒性 T 细胞反应的重要方面均受到 IFN3 的严格调节。我们开发了 IFN3 的小肽模拟物。 IFN3模拟物表现出针对多种病毒的抗病毒活性，包括在完整的IFN3因痘病毒产生的抗IFN蛋白而无效的条件下改善痘病毒痘苗对小鼠的致死作用。 IFN3 的激活作用受到细胞因子信号抑制蛋白 (SOCS) 的抑制，SOCS-1 是其中的重要成员。我们开发了一种小分子 SOCS-1 拮抗剂。在本次更新中，我们建议根据以下目标研究 IFN3、IFN3 模拟物和 SOCS-1 拮抗剂之间的相互作用，以积极调节免疫系统细胞的 IFN 反应，增强小鼠对痘苗病毒和节肢动物病毒的保护，从而开发出抗天花的 IFN 和 SOCS-1 拮抗剂药物。我们假设我们的小肽 IFN 模拟物和 SOSC-1 拮抗剂代表了针对致命痘病毒感染的新型抗病毒药物。 1.通过IFN模拟物保护小鼠免受致命痘苗病毒感染。 SOCS-1拮抗剂的保护作用。 2. 比较腹膜内施用与口服施用 IFN 模拟肽的相对能力，以了解其保护小鼠免受致命痘苗病毒感染的相对能力。 SOCS-1拮抗剂的作用。 3.通过IFN模拟物和SOCS-1拮抗剂保护小鼠免受致死性节肢动物病毒感染。 4.通过IFN模拟物和SOCS-1拮抗剂保护小鼠免受编码白细胞介素4(IL-4)基因的超致死性嗜好病毒的侵害。 5. 确定用 IFN 模拟物治疗小鼠的免疫学方面。 SOCS-1拮抗剂的作用。公共卫生相关性：我们的干扰素模拟物是一种治疗病毒和其他传染病的新型疗法。 SOCS-1 拮抗剂应该为增强免疫系统抵抗感染和癌症提供新的范例。