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A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells

A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells
A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells
MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-?, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-?, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-? and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions with other microRNAs when studying disease
genome scan, seasonal pollen sensitivity, asthma, atopy, linkage
1932-6203
e111659
Martinez-Nunez, Rocio T.
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Bondanese, Victor P.
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Louafi, Fethi
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Francisco-Garcia, Ana S.
a115c4da-3fd9-481f-98c9-404c8da338de
Rupani, Hitasha
ed650f59-d273-46e9-ac34-0cd179f494ca
Bedke, Nicole
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Holgate, Stephen
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Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
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Sanchez-Elsner, Tilman
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Martinez-Nunez, Rocio T.
a6069f08-55cf-4477-b895-9c4fdd2ee5ee
Bondanese, Victor P.
e25a2373-a26a-4f1d-880c-c88ca2c16d6b
Louafi, Fethi
75af1544-3c81-4a94-9bd3-50c2c74ad5c4
Francisco-Garcia, Ana S.
a115c4da-3fd9-481f-98c9-404c8da338de
Rupani, Hitasha
ed650f59-d273-46e9-ac34-0cd179f494ca
Bedke, Nicole
981dbd61-1912-4231-b6d5-42520c38178d
Holgate, Stephen
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Howarth, Peter H.
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Davies, Donna E.
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Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d

Martinez-Nunez, Rocio T., Bondanese, Victor P., Louafi, Fethi, Francisco-Garcia, Ana S., Rupani, Hitasha, Bedke, Nicole, Holgate, Stephen, Howarth, Peter H., Davies, Donna E. and Sanchez-Elsner, Tilman (2014) A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells. PLoS ONE, 9 (10), e111659. (doi:10.1371/journal.pone.0111659). (PMID:25360780)

Record type: Article

Abstract

MicroRNAs are short non-coding single stranded RNAs that regulate gene expression. While much is known about the effects of individual microRNAs, there is now growing evidence that they can work in co-operative networks. MicroRNAs are known to be dysregulated in many diseases and affect pathways involved in the pathology. We investigated dysregulation of microRNA networks using asthma as the disease model. Asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness and airway remodelling. The airway epithelium is a major contributor to asthma pathology and has been shown to produce an excess of inflammatory and pro-remodelling cytokines such as TGF-?, IL-6 and IL-8 as well as deficient amounts of anti-viral interferons. After performing microRNA arrays, we found that microRNAs -18a, -27a, -128 and -155 are down-regulated in asthmatic bronchial epithelial cells, compared to cells from healthy donors. Interestingly, these microRNAs are predicted in silico to target several components of the TGF-?, IL-6, IL-8 and interferons pathways. Manipulation of the levels of individual microRNAs in bronchial epithelial cells did not have an effect on any of these pathways. Importantly, knock-down of the network of microRNAs miR-18a, -27a, -128 and -155 led to a significant increase of IL-8 and IL-6 expression. Interestingly, despite strong in silico predictions, down-regulation of the pool of microRNAs did not have an effect on the TGF-? and Interferon pathways. In conclusion, using both bioinformatics and experimental tools we found a highly relevant potential role for microRNA dysregulation in the control of IL-6 and IL-8 expression in asthma. Our results suggest that microRNAs may have different roles depending on the presence of other microRNAs. Thus, interpretation of in silico analysis of microRNA function should be confirmed experimentally in the relevant cellular context taking into account interactions with other microRNAs when studying disease

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Accepted/In Press date: 25 September 2014
Published date: 31 October 2014
Keywords: genome scan, seasonal pollen sensitivity, asthma, atopy, linkage
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 380778
URI: https://eprints.soton.ac.uk/id/eprint/380778
ISSN: 1932-6203
PURE UUID: cbb098de-683e-4f8b-8a99-d92defd9b723
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 14 Sep 2015 13:38
Last modified: 03 Dec 2019 02:07

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