The emerging role of micro<scp>RNA</scp>s in regulating immune and inflammatory responses in the lung

Foster, Paul S.; Plank, Maximilian; Collison, Adam; Tay, Hock L.; Kaiko, Gerard E.; Li, Jingjing; Johnston, Sebastian L.; Hansbro, Philip M.; Kumar, Rakesh K.; Yang, Ming; Mattes, Joërg

doi:10.1111/imr.12058

Cited by 102 publications

(102 citation statements)

References 137 publications

(230 reference statements)

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“…These could involve other systemic responses such as conditioning of the BM, widespread and transportable inflammatory factors such as microRNAs and inflammasomes/ASC specks could be involved, and events may be exaggerated by infectious exacerbations of pulmonary disease (16,(71)(72)(73). These potential pathogenic processes could be examined using combinations of animal models and clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Fricker¹,

Goggins²,

Mateer³

et al. 2018

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Section: Discussionmentioning

confidence: 99%

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Fricker¹,

Goggins²,

Mateer³

et al. 2018

JCI Insight

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111

103

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“…36 miRs regulate cellular function by inhibiting mRNA translation and are important regulators of pulmonary inflammatory responses. 37 Of clinical relevance, miR-9 expression levels were also increased in sputum samples from neutrophilic steroid-resistant asthmatic patients. 36 Antagomir-mediated (antisense oligonucleotide) inhibition of miR-9 function restored Limited genetic diversity (fails to model differences in outbred human population) Well-established models of allergic/eosinophilic disease phenotypes Fewer models of non-allergic/neutrophilic phenotypes or acute exacerbations Access to tissues (e.g.…”

Section: Steroid Resistancementioning

confidence: 99%

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

et al. 2017

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Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are effective in relevant subsets of severe asthma patients. Unfortunately, non-allergic/noneosinophilic asthma, steroid resistance and disease exacerbation remain areas of unmet clinical need. No mouse model encompasses all features of severe asthma. However, mouse models can provide insight into pathogenic pathways that are relevant to severe asthma. In this review, as examples, we highlight models relevant to understanding steroid resistance, chronic tissue remodelling and disease exacerbation. Although these models highlight the complexity of the immune pathways that may underlie severe asthma, they also provide insight into new potential therapeutic approaches.

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“…Proinflammatory mediators (IL-1␤, TNF-␣, and Toll-like receptors) and monocytes/macrophages can also induce miR-155-5p expression (27,28). As one of the most well characterized miRNAs, miR-155-5p has more than 140 experimentally validated mRNA targets, including many key regulators of the inflammatory response (i.e., SHIP1, MYD88, FADD, INPP5D, SOCS1) (7,(29)(30)(31). A dual role for miR-155-5p as both an inhibitor and a mediator of inflammation has been described previously and is consistent with our data (7,30,31).…”

Section: Figmentioning

confidence: 99%

Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina

et al. 2015

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eThe mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs (miRNAs) are small noncoding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. Using a nonhuman primate model of choriodecidual infection, we sought to determine if differentially expressed miRNAs were associated with acute fetal lung injury. After inoculating 10 chronically catheterized pregnant monkeys (Macaca nemestrina) with either group B streptococcus (GBS) at 1 ؋ 10 6 CFU (n ‫؍‬ 5) or saline (n ‫؍‬ 5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled the changes in expression by microarray analysis. We identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of these, only miR-155-5p was validated by quantitative reverse transcription-PCR (P ‫؍‬ 0.02). Significantly elevated miR-155-5p expression was also observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-␣]). Overexpression of miR-155-5p in FeAE cells in turn increased the production of IL-6 and CXCL10/gamma interferon-induced protein 10, which are implicated in leukocyte recruitment but also in protection from lung injury. Interestingly, while miR-155-5p decreased fibroblast growth factor 9 (FGF9) expression in a luciferase reporter assay, FGF9 levels were actually increased in GBS-exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal lung development. Thus, upregulation of miR-155-5p may serve as a compensatory mechanism to lessen the increase in FGF9 and prevent aberrant lung development. Understanding the complicated networks regulating lung development in the setting of infection is a key step in identifying how to prevent fetal lung injury leading to bronchopulmonary dysplasia.

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The emerging role of microRNAs in regulating immune and inflammatory responses in the lung

Cited by 102 publications

References 137 publications

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina

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