miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli Anzola Santander, Andrea González Pérez, Raquel Gámez Belmonte, María de los Reyes Ocón, Borja Aranda, Carlos J. Martínez-Moya Bernal, Patricia López-Posadas, Rocío Hernández Chirlaque, Cristina Sánchez De Medina López-Huertas, Fermín Martínez Augustín, María Olga Regulation of miR-146a abundance and its role in intestinal inflammation and particularly in intestinal epithelial cells (IECs) has been poorly studied. Here we study the relationship between bacterial antigens and inflammatory stimuli, and miR-146a expression using IEC lines and models of colitis (trinitrobenzenesulfonic acid (TNBS), dextran sulfate sodium (DSS) and the CD4 + CD62L + T cell transfer model). Specific bacterial antigens and cytokines (LPS, flagelin and IL-1β/TNF) stimulate miR- 146a expression, while peptidoglycan, muramyldipeptide and CpG DNA have no effect. Overexpression of miR-146a by LPS depends on the activation of the TLR4/MyD88/NF-kB and Akt pathways. Accordingly, the induction of miR-146a is lower in TLR4, but not in TLR2 knock out mice in both basal and colitic conditions. miR-146a overexpression in IECs induces immune tolerance, inhibiting cytokine production (MCP-1 and GROα/IL-8) in response to LPS (IEC18) or IL-1β (Caco-2). Intestinal inflammation induced by chemical damage to the epithelium (DSS and TNBS models) induces miR-146a, but no effect is observed in the lymphocyte transfer model. Finally, we found that miR-146a expression is upregulated in purified IECs from villi vs. crypts. Our results indicate that miR-146a is a key molecule in the interaction among IECs, inflammatory stimuli and the microbiota. 2024-10-10T09:12:12Z 2024-10-10T09:12:12Z 2018-11-16 journal article Anzola, A., González, R., Gámez-Belmonte, R. et al. miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli. Sci Rep 8, 17350 (2018). https://doi.org/10.1038/s41598-018-35338-y https://hdl.handle.net/10481/95782 10.1038/s41598-018-35338-y eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Springer Nature