Type

Journal Article

Authors

Catherine M Greene
Noel G McElvaney
Catherine Mooney
Chiara De Santi
Tidi Hassan

Subjects

Biochemistry

Topics
genetics nf b rare diseases biomedical biotechnology alpha 1 antitrypsin aat augmentation therapy anti inflammatory twenty one clinical medicine monocytes therapy expression microrna expression alpha 1 antitrypsin

Alpha-1 antitrypsin augmentation therapy decreases miR-199a-5p, miR-598 and miR-320a expression in monocytes via inhibition of NFκB. (2017)

Abstract Alpha-1 antitrypsin (AAT) augmentation therapy involves infusion of plasma-purified AAT to AAT deficient individuals. Whether treatment affects microRNA expression has not been investigated. This study's objectives were to evaluate the effect of AAT augmentation therapy on altered miRNA expression in monocytes and investigate the mechanism. Monocytes were isolated from non-AAT deficient (MM) and AAT deficient (ZZ) individuals, and ZZs receiving AAT. mRNA (qRT-PCR, microarray), miRNA (miRNA profiling, qRT-PCR), and protein (western blotting) analyses were performed. Twenty one miRNAs were differentially expressed 3-fold between ZZs and MMs. miRNA validation studies demonstrated that in ZZ monocytes receiving AAT levels of miR-199a-5p, miR-598 and miR-320a, which are predicted to be regulated by NFκB, were restored to levels similar to MMs. Validated targets co-regulated by these miRNAs were reciprocally increased in ZZs receiving AAT in vivo and in vitro. Expression of these miRNAs could be increased in ZZ monocytes treated ex vivo with an NFκB agonist and decreased by NFκB inhibition. p50 and p65 mRNA and protein were significantly lower in ZZs receiving AAT than untreated ZZs. AAT augmentation therapy inhibits NFκB and decreases miR-199a-5p, miR-598 and miR-320a in ZZ monocytes. These NFκB-inhibitory properties may contribute to the anti-inflammatory effects of AAT augmentation therapy.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed
Ireland -> University College Dublin -> College of Science
Ireland -> University College Dublin -> Computer Science Research Collection
Ireland -> University College Dublin -> School of Computer Science

Full list of authors on original publication

Catherine M Greene, Noel G McElvaney, Catherine Mooney, Chiara De Santi, Tidi Hassan

Experts in our system

1
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Catherine Mooney
University College Dublin
Total Publications: 63
 
4
Chiara De Santi
Royal College of Surgeons in Ireland
Total Publications: 5
 
5
Tidi Hassan
Royal College of Surgeons in Ireland