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干扰素综述。

Interferon review.

作者信息

Stanton G J, Weigent D A, Fleischmann W R, Dianzani F, Baron S

出版信息

Invest Radiol. 1987 Mar;22(3):259-73. doi: 10.1097/00004424-198703000-00017.

Abstract

Although IFN proteins were recognized first for their potent antiviral properties, it has now been established that they may profoundly affect other vital cellular functions. The IFNs are divided into three main classes, alpha, beta, and gamma, and are defined by their differences in amino acid sequences, physicochemical properties, and induction by different agents from different cell types. The inducing agents include viruses, bacteria, bacterial products, polymers, low molecular weight compounds, and antigens or mitogens. Studies on the mechanisms of action of IFNs have mainly been focused on their antiviral actions. However, many of the facts revealed by these studies are equally relevant for understanding other actions of IFN. IFNs are extremely potent, they interact with specific receptors, and they induce the expression of specific genes, the products of which mediate their various actions. There is almost a complete lack of knowledge of what happens between the interaction of IFN with its receptor and induction of new RNA synthesis. However, we are beginning to understand how some of the IFN-inducible enzymes impair viral replication. The discovery of the dsRNA-dependent enzymes has implications beyond the IFN system. It is quite possible that they are used for other physiologic regulatory systems as well. The identities and functions of many other IFN-inducible proteins remain to be elucidated. Principally, IFNs alpha and beta are cytokines in that they may be produced by the cellular components of the immune system and have immunoregulatory effects on the cells of the immune system. These effects include enhancement of surface structures such as histocompatibility antigens, pleiotropic hormone-like effects, and stimulation or inhibition of the activities of a number of different effector cells such as B cells, T cells, macrophages, and natural killing cells. IFN levels may be below detection and yet mediate important biologic functions. Perhaps the most interesting IFN subtype regarding immunoregulation is IFN gamma, which is a product of T lymphocytes. Few drugs have stimulated as much research interest or clinical promise as the IFNs. Clinical trials in patients have shown most promise in coryza, herpes virus infections, papilloma virus tumors, hairy cell leukemia, multiple myeloma, and renal cell carcinoma. IFN gamma employed alone and in combination with IFN alpha may dramatically increase IFN's activity. IFN treatment combined with chemotherapy also may give enhanced antitumor activity.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

尽管干扰素蛋白最初因其强大的抗病毒特性而被认识,但现在已经确定它们可能会深刻影响其他重要的细胞功能。干扰素分为三大类,即α、β和γ,它们是根据氨基酸序列、理化性质以及不同细胞类型中不同诱导剂对其诱导作用的差异来定义的。诱导剂包括病毒、细菌、细菌产物、聚合物、低分子量化合物以及抗原或有丝分裂原。关于干扰素作用机制的研究主要集中在其抗病毒作用上。然而,这些研究揭示的许多事实对于理解干扰素的其他作用同样具有重要意义。干扰素极其强大,它们与特定受体相互作用,并诱导特定基因的表达,这些基因的产物介导其各种作用。对于干扰素与其受体相互作用以及新RNA合成诱导之间发生了什么,我们几乎一无所知。然而,我们开始了解一些干扰素诱导酶是如何损害病毒复制的。双链RNA依赖性酶的发现其意义超出了干扰素系统。很有可能它们也被用于其他生理调节系统。许多其他干扰素诱导蛋白的身份和功能仍有待阐明。主要地,α和β干扰素是细胞因子,因为它们可能由免疫系统的细胞成分产生,并对免疫系统的细胞具有免疫调节作用。这些作用包括增强表面结构,如组织相容性抗原,多效激素样作用,以及刺激或抑制许多不同效应细胞的活性,如B细胞、T细胞、巨噬细胞和自然杀伤细胞。干扰素水平可能低于检测阈值,但仍能介导重要的生物学功能。也许在免疫调节方面最有趣的干扰素亚型是γ干扰素,它是T淋巴细胞的产物。很少有药物能像干扰素那样激发如此多的研究兴趣或临床应用前景。对患者的临床试验表明,在治疗感冒、疱疹病毒感染、乳头瘤病毒肿瘤、毛细胞白血病、多发性骨髓瘤和肾细胞癌方面最有前景。单独使用γ干扰素以及与α干扰素联合使用可能会显著增强干扰素的活性。干扰素治疗与化疗联合使用也可能增强抗肿瘤活性。(摘要截选至400字)

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