The role of ATM in sodium butyrate-mediated inhibition of macrophage polarization

DNA damage response (DDR) signaling not only maintains genomic integrity but also plays a role in the activation of immune cells, including macrophages. In response to the stimuli, macrophages can be polarized into a proinflammatory phenotype, M1. In the monocytoid THP-1 cell-derived macrophage model, sodium butyrate was found to inhibit the expression of M1 biomarkers TNF-α, IL-6, IL-1β, and CXCL10, and downregulate DDR-associated proteins, including the apical Ataxia-Telangiectasia mutated protein kinase (ATM). However, siRNA-mediated knockdown of ATM did not reduce the expression of M1 biomarkers, but still downregulated the expression of DDR-associated proteins such as RAD50, p53, Chk1, NBS1, and γH2AX. Moreover, ATM knockdown modulated the expression of innate immunity regulatory genes, including sialic acid binding immunoglobulin type lectins 14 (Siglec14), Siglec15, signaling lymphocyte activation molecule family 1 (Siamf1), Siamf7, and guanylate binding protein 2 in response to the Infection of Mycobacterium tuberculosis H37Ra. The results suggest that ATM may serve as a regulator to couple the DDR and innate immune response of macrophages, but barely contributes to the sodium butyrate-mediated inhibition of certain M1 biomarkers.

ATM; DNA damage response (DDR); Macrophages; Mycobacterium tuberculosis; Polarization; Sodium butyrate.