Antituberculosis Action of the Synthetic Peptide LKEKK

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In this work, the activity of the synthetic peptide LKEKK was investigated in a mouse model of tuberculosis induced by Mycobacterium bivis-bovinus 8 strain. Therapy with peptide at doses of 0.01, 0.1 and 1 μg/kg (5 daily injections) significantly reduced the lung injury index of mice compared to animals in the control groups (no treatment and isoniazid treatment). Using [3H]LKEKK, it was shown that the high sensitivity of peritoneal macrophages and splenocytes of infected mice to the peptide was maintained for at least three weeks (Kd 18.6 and 16.7 nM for macrophage and splenocyte membranes, respectively).A study of cytokine production by splenocytes of infected mice showed that on the 24th day after treatment with the peptide (doses of 1 and 10 µg/kg) the secretion of IL-2 was restored to the level observed in uninfected animals. IFN-γ production by spleen cells of infected mice also significantly increased upon peptide treatment. At the same time, IL-4 production decreased in splenocytes. In addition, the peptide treatment stimulated the phagocytic activity of peritoneal macrophages, which was reduced due to tuberculosis infection. Thus, the synthetic peptide LKEKK increased the effectiveness of anti-tuberculosis therapy, as well as the strength of the immune response. The peptide can be used in complex therapy of tuberculosis.

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作者简介

E. Navolotskaya

Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

编辑信件的主要联系方式.
Email: navolotskaya@bibch.ru
俄罗斯联邦, prosp. Nauki 6, Pushchino, 142290

D. Zinchenko

Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Email: navolotskaya@bibch.ru
俄罗斯联邦, prosp. Nauki 6, Pushchino, 142290

A. Kolobov

State Research Center for Institute of Highly Pure Bioprepararions, FMBA of the Russian Federation

Email: navolotskaya@bibch.ru
俄罗斯联邦, ul. Pudozhskaya 7, St. Petersburg 197110

Y. Zolotarev

Institute of Molecular Genetics, Russian Academy of Science

Email: navolotskaya@bibch.ru
俄罗斯联邦, pl. akad. Kurchatova 2, Moscow, 123182

A. Murashev

Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry

Email: navolotskaya@bibch.ru
俄罗斯联邦, prosp. Nauki 6, Pushchino, 142290

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2. 1. Dependence of the total (1), specific (2), and non-specific (3) binding of the [3H]LACKE peptide to the membranes of mouse peritoneal macrophages (a) and splenocytes (b) on incubation time. The amount of specific binding of the labeled peptide was determined as the difference between its general and non-specific binding.

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3. Fig. 2. Analysis in Scatchard coordinates of the specific binding of the [3H]LKEKK peptide to the plasma membranes of peritoneal macrophages (1) and splenocytes (2) of intact mice (a) and mice infected with M. bovis-bovinus 8 (b). B and F are the molar concentrations of bound and free labeled peptide [3H]LKEKK, respectively.

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