Study of gamma interferon agonists/mimetics

γ干扰素激动剂/模拟物的研究

• 批准号: 7445465
• 负责人: HOWARD M JOHNSON
• 金额: $ 36.63万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7445465
• 关键词: Agonist; Antiviral Agents; CD4 Positive T Lymphocytes; Cells; Condition; Cytokine Inducible SH2-Containing Protein; Cytotoxic T-Lymphocytes; Exhibits; Helper-Inducer T-Lymphocyte; Immune system; Immunity; Infection; Interferon Type II; Interferons; Macrophage Activation; Malignant Neoplasms; Mediation; Medical Surveillance; Mouse Pox Virus; Mus; Natural Immunity; Natural Killer Cells; Oral Administration; Peptides; Pharmaceutical Preparations; Poxviridae; Poxviridae Infections; Proteins; Relative (related person); Smallpox; Vaccinia; Vaccinia virus; Virus; Virus Diseases; cytokine; immune function; intraperitoneal; member; mimetics; novel; response; small molecule

Gamma interferon 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 IFN gamma. We have developed small peptide mimetics of IFN gamma. The IFN gamma 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 IFN gamma is ineffective because of anti-IFN proteins produced by poxviruses. The activating effects of IFN gamm are suppressed by proteins called suppressors of cytokine signaling (SOCS), of which SOCS-1 is an important member. We have developed small molecule mimetics of SOCS-1 as well as a small molecule SOCS-1 antagonist. In this renewal, we propose to study the interaction between IFN gamma, IFN gamma mimetics, SOCS-1 mimetics, and SOCS-1 antagonists as per AIMs below to positively and negatively 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 drug against smallpox. We hypothesize that our small peptide IFN mimetics represent novel antivirals against lethal poxvirus infections. 1. Protection of mice against lethal vaccinia virus infections by IFN mimetics. Effect of SOCS-1 mimetics and their antagonists 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 antagonists. 4. Determine immunological aspects of treatment of mice with IFN mimetics. Effect of SOCS-1 antagonist.

γ干扰素是一种重要的细胞因子，用于介导对监测至关重要的免疫功能 对抗感染和癌症。先天免疫、适应性免疫、巨噬细胞 活化、自然杀伤细胞活性、辅助性T细胞应答以及细胞毒性T细胞应答都是 受到IFN γ的严格调节。我们已经开发了IFN γ的小肽模拟物。的IFN γ模拟物表现出抗多种病毒的抗病毒活性， 痘病毒牛痘在小鼠中的作用是在完整的IFN γ由于以下原因而无效的条件下， 痘病毒产生的抗干扰素蛋白。IFN γ的激活作用被蛋白质抑制 称为细胞因子信号转导抑制因子（SOCS），SOCS-1是其中的重要成员。我们有 开发了SOCS-1的小分子模拟物以及小分子SOCS-1拮抗剂。在这 更新，我们建议研究IFN γ，IFN γ模拟物，SOCS-1模拟物， 和SOCS-1拮抗剂，以正向和负向调节细胞的IFN应答 的免疫系统和增强保护小鼠对牛痘和鼠痘病毒与 一种对抗天花的干扰素药物。我们假设我们的小肽IFN模拟物代表了 针对致死性痘病毒感染的新型抗病毒药。 1. IFN模拟物保护小鼠免受致死性牛痘病毒感染。SOCS-1模拟物的作用 和他们的对手保护。 2.比较腹膜内与口服施用IFN模拟肽的相对能力， 保护小鼠免受致命的牛痘病毒感染。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肢脱病病毒感染。 4.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。