Biomedical Chemistry: Research and Methods 2027, 7(1), e00208

Rifampicin inhibits TLR4 and IL1β gene expression and enhances SH-SY5Y cell viability after prolonged ethanol exposure in an in vitro experiment

M.I. Airapetov1,2, S.O. Eresko1,3, Rogova A.C.4,5, E.R. Bychkov1, A.A. Lebedev1, P.D. Shabanov1,2

1Institute of Experimental Medicine, 12 Acad. Pavlova str., St. Petersburg, 197376 Russia

2Kirov Military Medical Academy, St. Petersburg, Russia

3North-Western State Medical University named after I.I. Mechnikov, St. Petersburg, Russia

4Saint-Petersburg National Research University of Information Technologies, Mechanics and Optics, St. Petersburg, Russia

5Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia

Keywords:peptide retention time; isoelectric point; post-translational modifications; web service

DOI:10.18097/BMCRM00208

The whole version of this paper is available in Russian.

Prolonged alcohol exposure activates TLR4-signaling pathways in the brain, which is responsible for the development of neuroinflammation. There is interest in pharmacologic correction of these mechanisms. The antibiotic rifampicin (Rif) has established itself as a potential neuroprotectant in studies on its use to correct various pathologic conditions of the nervous system associated with the development of neuroinflammatory events. We performed a study on human neuroblastoma cell culture SH-SY5Y. Prolonged incubation of cells in ethanol (24 h, 100 mM) of SH-SY5Y induces activation of the innate immune system genes Tlr4 and Il1β. Pre-addition of rifampicin (25-100 mM) prior to incubation of cells in ethanol solution inhibited Tlr4 and Il1β gene expression, whereas addition of rifampicin after incubation of cells in ethanol dose-dependently reduced the increased expression of Tlr4 and Il1β genes, with the most significant effect at a concentration of 100 mM. In addition, the use of rifampicin increased cell survival in culture. Thus, the results of our experiment showed that Rif is able to eliminate the increased expression of inflammation genes caused by prolonged alcohol exposure and to increase the survival rate of long-term incubated cells in ethanol solution.
Figure 1. Viability of SH-SY5Y culture after 24 h incubation in ethanol solution (100 mM) and after 2 h incubation with DMSO and Rif (*p≤0.05 vs. ethanol).
Figure 2. Relative level of TLR4 (left) and IL1β (right) mRNA content (*p≤0.05 vs. control, #p≤0.05 vs. ethanol).
Figure 3. Putative mechanism of action of Rif.

CLOSE
Table 1. Sequence of primers.

FUNDING

The work was carried out within the framework of the State Task of the Ministry of Education and Science of Russia (2022-2025) “Search for molecular targets for pharmacological effects in addictive and neuroendocrine disorders and the creation of new pharmacologically active substances acting on CNS receptors”, code FGWG-2022-0004.

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