Application of metallothionein-1 in preparation of medicine for treating bacterial infection
A technology for bacterial infection and inhibition of bacteria, applied in antibacterial drugs, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve the problems of escaping antibiotic inhibition and killing, and achieve the effect of reducing mortality
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Embodiment 1
[0040] Example 1 LM infection of HepG2 cells significantly induced the expression of inflammatory cytokines and MT1a
[0041] Overexpression of metallothionein-1 and recombinant proteins inhibit inflammation in autoimmune diseases, promote the differentiation of regulatory T cells and reduce the expression of innate and acquired immune inflammatory factors, suggesting that the expression of metallothionein is inhibited and metallothionein is down-regulated Protein levels can be upregulated by mechanisms of immunity. Small molecule protein MT is widely involved in heavy metal detoxification and free radical scavenging, and studies have shown that MT protein has immune regulation function. In order to study the role of MT in LM infection, the effect of LM infection on the expression of MT in hepatocytes was first analyzed (hepatocytes have been shown to highly express MT).
[0042] We learned from GEPIA database and Human Protein Atlas that Mt1a, Mt1h, and Mt2a are highly expre...
Embodiment 2
[0082] Example 2 Knocking out the MT1 gene reduces the bacterial load of LM in mouse liver and spleen
[0083] MT1 is rich in Cys, which can maintain the level of intracellular heavy metals, especially zinc ions, through the combination and release of sulfhydryl groups and zinc ions, and remove active oxygen through redox cycles; down-regulating the expression of MT1 will reduce intracellular zinc ions and increase intracellular activity The level of free radicals such as oxygen, while zinc ions are essential nutrients for the proliferation of LM and many bacteria, free radicals have a killing effect on LM. In recent years, metallothionein has emerged as an important, but largely underappreciated component of the immune system. MTs have been shown to participate in the regulation of innate and adaptive immunity through the regulation of heavy metal ions and redox status in immune cells, as well as through the regulation of various immune-related cytokines and transcripts. Inc...
Embodiment 3
[0207] Example 3 Knocking out the MT1 gene reduces the lethality of Listeria monocytogenes-infected mice
[0208] One, experimental material and reagent are identical with embodiment 2;
[0209] 2. Experimental method:
[0210] 1. The establishment of the systemic infection model of Listeria monocytogenes live bacteria is the same as in Example 2;
[0211] 2. Live Listeria monocytogenes infection of MT1 - / - After mixing with WT mice, the body weight of the mice was recorded every day, and the symptoms and signs of the mice and whether they died were observed.
[0212] 3. Experimental results
[0213] 1. Knocking out the MT1 gene reduces the weight loss of mice caused by LM infection
[0214] To further study MT1 - / - In the role of LM infection, this embodiment uses 6.5x10 5 cfu LM infection of WT mice and Mt1 - / - After 60 hours of the mice, the body weight changes of the mice were observed. The results showed that in LM-infected mice, compared with wild-type mice, MT1 ...
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