TY - JOUR
T1 - miR-146a regulates the crosstalk between intestinal epithelial cells, microbial components and inflammatory stimuli
AU - Anzola, Andrea
AU - González, Raquel
AU - Gámez-Belmonte, Reyes
AU - Ocón, Borja
AU - Aranda, Carlos J.
AU - Martínez-Moya, Patricia
AU - López-Posadas, Rocío
AU - Hernández-Chirlaque, Cristina
AU - Sánchez de Medina, Fermín
AU - Martínez-Augustin, Olga
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85057259887&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-35338-y
DO - 10.1038/s41598-018-35338-y
M3 - Article
C2 - 30478292
AN - SCOPUS:85057259887
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 17350
ER -