Publications

Authors:

Rossato, Marzia; Bazzoni, Flavia; Gaudiosi, D.; Mirolo, M.; Fabbrim, ; Mori, L.; Tamassia, Nicola; Mantovani, A.; Cassatella, Marco Antonio; Locati, M.

Title:

A regulatory circuitry involving microRNA-9 and NF-kB controls neutrophil and monocyte activation in response to LPS

Year:

2009

Type of item:

Contributo in atti di convegno

Tipologia ANVUR:

Contributo in Atti di convegno

Language:

Inglese

Format:

A Stampa

Congresso:

2nd european congress of immunology

Place:

Berlino, Germania

Period:

13-16 settembre 2009

Keyword:

inflammation; innate immunity; Toll-like receptors; cytokines; NFKB1

Short description of contents:

Objectives: Recent studies have shown that microRNAs (miRNAs) contribute to the regulation of inflammation by repressing gene expression at the posttranscriptional level. In this study, we investigated the potential involvement of miRNAs in the regulation of innate immune response by evaluating the profile of miRNAs expressed in human polymorphonuclear neutrophils (PMN) and monocytes after TLR4 engagement. Methods: A TaqMan-based Array was utilized to identify miRNAs modulated by LPS in human PMN and monocytes. Analysis of the mechanisms controlling the expression of miR-9 and of its precursor (pri-miR-9) was subsequently performed by RT-qPCR. Computational predictions obtained from the miRGen database, together with cotransfection experiments of miR-9 with 3’UTR luciferase reporters identified NFKB1 as miR-9 target. The expression profile of endogenous NFKB1 was analyzed at the transcriptional and protein levels in PMN and monocytes stimulated with LPS and in miR-9 overexpressing monocytes. Results: Screening for miRNA expressed in human monocytes exposed to LPS highlighted the induction of miRNAs previously described in myeloid cell lines, namely miR-146, miR-155, miR-132, and uncovered the induction of previously unrecognized miRNAs, including miR-187, the miR-125a/miR-99b/let-7e cluster, and miR-9/9*. Interestingly, out of the 384 tested, miR-9/9* were the only miRNAs induced by LPS also in human PMN. Among the three different genes encoding miR-9 precursors in humans, LPS selectively induced the transcription of pri-miR-9-1 in a MyD88- and NF-kB-dependent manner. Both in PMN and monocytes, LPS regulated NFKB1 both at the transcriptional and post-transcriptional levels, and a conserved miR-9 seed sustained a miR-9-dependent inhibition of the NFKB1 transcript. Finally, NFKB1 expression was reduced in monocytes overexpressing miR-9. Conclusion: In the present study, we identify miR-9 as an LPS-responsive miRNA in primary human PMN and monocytes, providing the first evidence linking miR-9 to the innate immune response. In addition, the identification of NFKB1 as a miR-9 target gene suggests a model whereby TLR4-activated NF-kB rapidly increases the expression of miR-9. In turn, this latter operates a feed-back control by fine tuning the expression of NFKB1, preventing in this manner the negative regulation by NFKB1/p50 homodimers as occurs in monocytes in systemic anti-inflammatory response syndrome and in cancer.

Product ID:

56464

Handle IRIS:

11562/342637

Deposited On:

May 19, 2010

Last Modified:

November 3, 2022

Bibliographic citation:

Rossato, Marzia; Bazzoni, Flavia; Gaudiosi, D.; Mirolo, M.; Fabbrim, ; Mori, L.; Tamassia, Nicola; Mantovani, A.; Cassatella, Marco Antonio; Locati, M., A regulatory circuitry involving microRNA-9 and NF-kB controls neutrophil and monocyte activation in response to LPS , Proceedings of "2nd european congress of immunology" , Berlino, Germania , 13-16 settembre 2009 , 2009

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