Application of metallothionein-1 in preparation of drugs for inhibiting rheumatoid arthritis

A metallothionein, rheumatoid technology, applied in metallothionein, drug combination, peptide/protein components, etc., can solve the problems of limited efficacy of rheumatism drugs, increased disability rate of RA patients, lack of effective treatment methods, etc. , to reduce clinical scores, expand social and economic value, and reduce the incidence of CIA

Active Publication Date: 2017-09-19
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] At present, there is still a lack of effective treatment methods for RA joint destruction in medicine. Most of the drugs for rheumatism have limited curative effect, large side effects and poor progn...

Method used

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  • Application of metallothionein-1 in preparation of drugs for inhibiting rheumatoid arthritis
  • Application of metallothionein-1 in preparation of drugs for inhibiting rheumatoid arthritis
  • Application of metallothionein-1 in preparation of drugs for inhibiting rheumatoid arthritis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1: Experiment of Up-regulation of MT1 Expression in RA

[0066] The small molecular protein MT1 can be widely involved in heavy metal detoxification and free radical scavenging, and studies have shown that MT1 protein has a potential immune regulatory function outside the cell. In order to study the role of MT1 in RA, its expression in RA samples was firstly analyzed, and this embodiment will carry out in-depth research by means of cell biology and molecular biology.

[0067] 1. Experimental materials and reagents

[0068] 1. Experimental Materials

[0069] DBA mice were raised in the SPF animal center of Shenzhen University; PBMC cells were cultured with RPMI 1640 (10% FBS) medium; RT-PCR primers were synthesized at Shanghai Sangon Bioengineering Co., Ltd.; fluorescent quantitative PCR instrument was purchased from 7500fast, Applied Biosystem, USA; Other instrument consumables: gun tips, test tubes, centrifuge tubes, volumetric bottles, measuring cups, beakers...

Embodiment 2

[0178] Example 2: Test of MT1 inhibiting the occurrence and development of CIA

[0179] The CIA animal model is currently recognized as a typical model for the study of RA, and its phenotype is very similar to the clinical symptoms of RA. In this example, in order to further study the regulatory effect of MT1 on the process of RA, I used local injection of adenovirus expressing MT1 in CIA mice to observe the regulatory effect of MT1 on the phenotypes such as CIA process, clinical score, and synovial inflammation.

[0180] 1. Experimental materials and reagents

[0181] 1. Experimental Materials

[0182] Same as embodiment one.

[0183] . experimental reagent

[0184] MT1 recombinant protein was donated by Shenzhen Yidakai Company; IL-1β, TNFα, IFNγ, IL-17A and IL-6 ELISA kits were purchased from eBioscience Company.

[0185] All the other are the same as embodiment one.

[0186] 2. Experimental method

[0187] 1. Construction of Adenoviral Vectors

[0188] Using Invi...

Embodiment 3

[0239] Example 3: Experiment of MT1 Regulating Th17 / Treg Balance

[0240] The stability of the immune environment depends on the balance between Th / Treg cells, and the abnormal content or function of these cells will lead to the occurrence of autoimmune diseases. The discovery of Th17 cells originated from the research on the mechanism of autoimmune diseases. Th17 cells mainly secrete cytokines such as IL-17A, IL-17F, and IL-22, which regulate inflammatory responses and promote autoimmune diseases. On the contrary, Treg cells maintain the stability of the immune system and inhibit the occurrence of autoimmune diseases by regulating the function of effector Th cells. The immunological mechanism of RA has not yet been clarified, but studies have shown that Th17 cell differentiation and Treg cell dysfunction are closely related to the occurrence of RA. Therefore, this example examines that MT-1 inhibits the occurrence and development of RA by regulating the balance of Th17 / Treg ...

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PUM

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Abstract

The invention discloses application of metallothionein-1 in the preparation of drugs for inhibiting rheumatoid arthritis. The metallothionein-1 inhibits the differentiation of Th17 cells, promotes the differentiation of regulatory T cells, regulates the balance of Th17/Treg under the state of CIA, and participates in the generation and development of rheumatoid arthritis; and the metallothionein-1 inhibits the expression of various inflammatory factors related to rheumatoid arthritis by a negative feedback regulation mechanism, and promotes the expression of immune suppression factors (IL-10 and TGF-beta) by a positive feedback regulation mechanism, and therefore, inflammatory response and pathologic change of rheumatoid arthritis are reduced, the process of the rheumatoid arthritis is delayed, and clinical evidence and a drug target are provided for the diagnosis and treatment of autoimmune diseases related to rheumatoid arthritis.

Description

technical field [0001] The invention relates to the field of medicine, especially metallothionein-1 recombinant protein, metallothionein-1 recombinant protein-immune protein G-FC fusion protein, and hyaluronic acid-wrapped metallothionein-1 recombinant protein and metallothionein -1 Preparation of recombinant protein-immune protein G-FC fusion protein nanoparticles, and its application in the treatment of rheumatoid arthritis and other autoimmune diseases. Background technique [0002] The stability of the body's immune environment depends on the balance between pro-inflammatory Th cells (cTh) and anti-inflammatory Treg cells. The immune balance between cTh / Treg cells is disturbed. For example, excessive activation of cTh cells can lead to autoimmune diseases. occur. Rheumatoid arthritis (RA) is a multi-joint systemic autoimmune disease characterized by chronic synovial inflammation, which eventually leads to joint destruction and physical disability. Although its specific...

Claims

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Application Information

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IPC IPC(8): C12N15/70C12N15/81C07K14/825A61K38/17A61P29/00A61P19/02A61P19/08A61P37/02A61P17/06A61P9/10A61P3/04A61P1/00
CPCA61K38/00C07K14/825C12N15/70C12N15/81
Inventor 黄钟孙锦霞
Owner SHENZHEN UNIV
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