High-Frequency Repetitive Magnetic Stimulation Activates Bactericidal Activity of Macrophages via Modulation of p62/Keap1/Nrf2 and p38 MAPK Pathways

Thérèse B. Deramaudt (1) , Ahmad Chehaitly (1) , Théo Charrière (1) , Julie Arnaud (1) , Marcel Bonay (1, 2)

1 END-ICAP - Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées
2 Hôpital Ambroise Paré [AP-HP]

The effects of repetitive magnetic stimulation (rMS) have predominantly been studied in excitable cells, with limited research in non-excitable cells. This study aimed to investigate the impact of rMS on macrophages, which are crucial cells in the innate immune defense. THP-1-derived macrophages subjected to a 5 min session of 10 Hz rMS exhibited increased Nrf2 activation and decreased Keap1 expression. We found that activation of the Nrf2 signaling pathway relied on rMS-induced phosphorylation of p62. Notably, rMS reduced the intracellular survival of Staphylococcus aureus in macrophages. Silencing Nrf2 using siRNA in THP-1-derived macrophages or utilizing Nrf2 knockout in alveolar macrophages abolished this effect. Additionally, rMS attenuated the expression of IL-1β and TNF-α inflammatory genes by S. aureus and inhibited p38 MAPK activation. These findings highlight the capacity of rMS to activate the non-canonical Nrf2 pathway, modulate macrophage function, and enhance the host’s defense against bacterial infection.

Keywords: alveolar macrophages; Keap1; Nrf2; Nrf2 knockout mice; p38 MAPK; p62; repetitive magnetic stimulation; Staphylococcus aureus; THP-1-derived macrophages

Domains: Life Sciences [q-bio]

Thérèse B. Deramaudt, Ahmad Chehaitly, Théo Charrière, Julie Arnaud, Marcel Bonay. High-Frequency Repetitive Magnetic Stimulation Activates Bactericidal Activity of Macrophages via Modulation of p62/Keap1/Nrf2 and p38 MAPK Pathways. Antioxidants , 2023, 12 (9), ⟨10.3390/antiox12091695⟩. ⟨hal-04229523⟩