An appropriate immune response requires a tight balance between pro-and anti-inflammatory mechanisms. IL-10 is induced at late time-points during acute inflammatory conditions triggered by TLR-dependent recognition of infectious agents and is involved in setting this balance, operating as a negative regulator of the TLR-dependent signaling pathway. We identified miR-125a similar to 99b similar to let-7e as an evolutionary conserved microRNA cluster late-induced in human monocytes exposed to the TLR4 agonist LPS as an effect of this IL-10-dependent regulatory loop. We demonstrated that microRNAs generated by this cluster perform a pervasive regulation of the TLR signaling pathway by direct targeting receptors (TLR4, CD14), signaling molecules (IRAK1), and effector cytokines (TNF alpha, IL-6, CCL3, CCL7, CXCL8). Modulation of miR-125a similar to 99b similar to let-7e cluster influenced the production of proinflammatory cytokines in response to LPS and the IL-10-mediated tolerance to LPS, thus identifying this gene as a previously unrecognized major regulatory element of the inflammatory response and endotoxin tolerance.
Multi-Step Regulation of the TLR4 Pathway by the miR-125a~99b~let-7e Cluster / G. Curtale, T. Renzi, M. Mirolo, L. Drufuca, M. Albanese, M. De Luca, M. Rossato, F. Bazzoni, M. Locati. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 9:(2018 Sep 02), pp. 2037.1-2037.16. [10.3389/fimmu.2018.02037]
Multi-Step Regulation of the TLR4 Pathway by the miR-125a~99b~let-7e Cluster.
M. Albanese;M. Locati
Ultimo
2018
Abstract
An appropriate immune response requires a tight balance between pro-and anti-inflammatory mechanisms. IL-10 is induced at late time-points during acute inflammatory conditions triggered by TLR-dependent recognition of infectious agents and is involved in setting this balance, operating as a negative regulator of the TLR-dependent signaling pathway. We identified miR-125a similar to 99b similar to let-7e as an evolutionary conserved microRNA cluster late-induced in human monocytes exposed to the TLR4 agonist LPS as an effect of this IL-10-dependent regulatory loop. We demonstrated that microRNAs generated by this cluster perform a pervasive regulation of the TLR signaling pathway by direct targeting receptors (TLR4, CD14), signaling molecules (IRAK1), and effector cytokines (TNF alpha, IL-6, CCL3, CCL7, CXCL8). Modulation of miR-125a similar to 99b similar to let-7e cluster influenced the production of proinflammatory cytokines in response to LPS and the IL-10-mediated tolerance to LPS, thus identifying this gene as a previously unrecognized major regulatory element of the inflammatory response and endotoxin tolerance.File | Dimensione | Formato | |
---|---|---|---|
fimmu-09-02037.pdf
accesso aperto
Tipologia:
Publisher's version/PDF
Dimensione
4.12 MB
Formato
Adobe PDF
|
4.12 MB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.