RT Journal Article
T1 miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli.
A1 Anzola, Andrea
A1 Gonzalez, Raquel
A1 Gamez-Belmonte, Reyes
A1 Ocon, Borja
A1 Aranda, Carlos J
A1 Martinez-Moya, Patricia
A1 Lopez-Posadas, Rocio
A1 Hernandez-Chirlaque, Cristina
A1 Sanchez de Medina, Fermin
A1 Martinez-Augustin, Olga
K1 Animals
K1 Cell Line
K1 Colitis
K1 Epithelial Cells
K1 Female
K1 Flagellin
K1 Gastrointestinal Microbiome
AB 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.
PB Nature Publishing Group
YR 2018
FD 2018-08-14
LK http://hdl.handle.net/10668/13241
UL http://hdl.handle.net/10668/13241
LA en
NO Anzola A, González R, Gámez-Belmonte R, Ocón B, Aranda CJ, Martínez-Moya P, et al. miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli. Sci Rep. 2018 Nov 26;8(1):17350.
NO Grant support: this work was supported by funds from the Ministerio de Economía y Competitividad and the Fondo Europeo de Desarrollo Regional FEDER (SAF2008-01432, AGL2008-4332, SAF2011-22922, SAF2011-22812, BFU2014-57736-P, AGL2014-58883-R, AGL2017-85270-R, SAF2017-88457-R) and from Junta de Andalucía (CTS164, CTS235 and CTS6736). AA was supported by fellowships from the Junta de Andalucía and the University of Granada. BO, CJA, PMM, RLP, CHC and RGB were supported by fellowships from the Ministery of Education and the University of Granada. RG was supported by CIBERehd, which is funded by Instituto de Salud Carlos III. In addition to the sources of funding acknowledged, the authors have received support from: Amino Up Chemical, Biosearch, Bioiberica, APC Europe, Sanofi, Hospira, Pzifer, and Hojiblanca.
DS RISalud
RD Apr 18, 2025