The immunoproteasome inhibitor ONX-0914 regulates inflammation and expression of contraction associated proteins in myometrium

S Liong; R Lim; C Nguyen-Ngo; G Barker; HC Parkington; M Lappas

Journal article

The immunoproteasome inhibitor ONX-0914 regulates inflammation and expression of contraction associated proteins in myometrium

S Liong, R Lim, C Nguyen-Ngo, G Barker, HC Parkington, M Lappas

European Journal of Immunology | WILEY | Published : 2018

DOI: 10.1002/eji.201747458

Download PDF

Abstract

There are currently no effective treatments to prevent spontaneous preterm labor. The precise upstream biochemical pathways that regulate the transition between uterine quiescence during pregnancy and contractility during labor remain unclear. It is well known however that intrauterine inflammation, including infection, is commonly associated with preterm labor. In this study, we identified the immunoproteasome subunit low-molecular-mass protein (LMP)7 mRNA expression to be significantly upregulated in laboring human myometrium. Silencing LMP7 using siRNA-targeted knockdown of LMP7 and its inhibitor ONX-0914 in human myometrial cells and tissues decreased proinflammatory cytokines (IL-6), ce..

View full abstract

University of Melbourne Researchers

Martha Lappas Author

Related Projects (2)

UNDERSTANDING THE MECHANISMS THAT REGULATE INFECTION-INDUCED PRETERM BIRTH

Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of th..

UNDERSTANDING WHAT TRIGGERS BIRTH

Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of th..

Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

The following are gratefully acknowledged: clinical research midwives Genevieve Christophers, Gabrielle Fleming, and Rachel Murdoch for sample collection; and the obstetrics and midwifery staff of the Mercy Hospital for Women for their cooperation. M.L. is supported by a Career Development Fellowship from the National Health and Medical Research Council (NHMRC; grant no. 1047025) and Research Fellowship from the University of Melbourne. S.L. was supported by a Glyn White Research Fellowship by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Research Foundation. C.N.N. was supported by an Australian Government Research Training Program (RTP) Scholarship. This study was supported by the Norman Beischer Medical Research Foundation, The University of Melbourne and the Mercy Research Foundation. Part of this work was supported by the National Health & Medical Research Council (NHMRC) project grants (1058786 to M.L. 1042478 to H.C.P.).