miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production

Weldon, Sinéad; McNally, Paul; McAuley, Daniel F.; Oglesby, Irene; Wohlford‐Lenane, Christine L.; Bartlett, Jennifer; Scott, Christopher J.; McElvaney, Noel G.; Greene, Catherine M.; McCray, Paul B.; Taggart, Clifford C.

doi:10.1164/rccm.201311-1986oc

Cited by 74 publications

(85 citation statements)

References 54 publications

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“…Interestingly, a recent study by Weldon et al (2014), has revealed a new mechanism through which cathepsin S expression becomes elevated in CF BAL fluid of nonPseudomonas aeruginosa infected patients. Epithelial cells were found to drive expression of the protease in an IRF-1 dependent manner that was a result of the loss of miR-31 which negatively regulates the expression of this transcription factor (Weldon et al, 2014).…”

Section: Cystic Fibrosismentioning

confidence: 99%

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Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

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168

139

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Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.

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Section: Cystic Fibrosismentioning

confidence: 99%

“…Epithelial cells were found to drive expression of the protease in an IRF-1 dependent manner that was a result of the loss of miR-31 which negatively regulates the expression of this transcription factor (Weldon et al, 2014).…”

Section: Cystic Fibrosismentioning

confidence: 99%

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Wilkinson

Williams

Scott

et al. 2015

Biological Chemistry

Self Cite

168

139

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“…IRF1 is frequently part of TLR signalling as it can be activated directly downstream from TLR2 [54]. However, in this study, cathepsin S transcription was not found to be dependent on P. aeruginosa infection [53]. Although not further investigated in this study, TLR2 activation and subsequent cathepsin S transcription by IRF1 could still potentially exist through infection by Staphylococcus aureus , a potent trigger of TLR2 signalling and a common resident pathogen in CF lungs [54].…”

Section: Mirnas Cf and Tlrsmentioning

confidence: 94%

“…Weldon et al [53 ]found a significant increase of cathepsin S in the bronchoaveolar lavage fluid of CF patients over that from non-CF lungs. Together with neutrophil elastase, this potent protease and pro-inflammatory mediator is thought to be an important exacerbator of lung tissue destruction and inflammation.…”

Section: Mirnas Cf and Tlrsmentioning

confidence: 99%

Toll-Like Receptors in Cystic Fibrosis: Impact of Dysfunctional microRNA on Innate Immune Responses in the Cystic Fibrosis Lung

Vencken

Greene²

2016

J Innate Immun

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Toll-like receptors (TLRs) are a class of pattern recognition receptors that are particularly expressed in the sentinel and epithelial cells in the body, including the lung. They are central players in the innate immune system in response to microbial infection, and are the triggers of a complex pathway network that both promotes the inflammatory response and influences the adaptive immune response. These pathways are transiently and finely tuned by cellular factors, including a cell's microRNA response program. MicroRNAs are small, non-coding RNAs that specifically regulate gene expression. In this article, we review the disease-specific microRNA regulatory network of cystic fibrosis, a debilitating and ultimately fatal disease and, specifically, its effect on TLR signalling.

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“…For example, during influenza A infection, upregulation of miR-136 promotes IFN-β accumulation in an A549 epithelial cell model, promoting viral killing [35] . In response to bacteria such as Mycobacterium bovis , Staphylococcus aureus , or Pseudomonas aeruginosa altered expression of miR-21, miR-124, and miR-93 regulates production of inflammatory cytokines, such as IL-8, by the epithelium [36][37][38] .…”

Section: Epitheliummentioning

confidence: 99%

Role of MicroRNA in the Lung's Innate Immune Response

Cohen¹

2016

J Innate Immun

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The immune response to respiratory pathogens must be robust enough to defend the host yet properly constrained such that inflammation-induced tissue damage is avoided. MicroRNA (miRNA) are small noncoding RNA which posttranscriptionally influence gene expression. In this review, we discuss recent experimental evidence of the contribution of miRNA to the lung's response to bacterial and viral pathogens.

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miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production

Abstract: Rationale: Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the b-defensin family.

Cited by 74 publications

References 54 publications

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Cathepsin S: therapeutic, diagnostic, and prognostic potential

Toll-Like Receptors in Cystic Fibrosis: Impact of Dysfunctional microRNA on Innate Immune Responses in the Cystic Fibrosis Lung

Role of MicroRNA in the Lung's Innate Immune Response

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