Journal article
Cystathionine-gamma-lyase gene silencing with siRNA in monocytes/macrophages protects mice against acute pancreatitis
Applied microbiology and biotechnology, Vol.100(1), pp.337-346
01/01/2016
DOI: 10.1007/s00253-015-6989-z
PMID: 26411454
Abstract
Hydrogen sulphide (H2S) is an endogenous inflammatory mediator produced by cystathionine-gamma-lyase (CSE) in monocytes/macrophages. To determine the role of H2S and macrophages in inflammation, we used small interference RNA (siRNA) to target the CSE gene and investigated its effect in a mouse model of acute pancreatitis. Acute pancreatitis is characterised by increased levels of plasma amylase, myeloperoxidase (MPO) activity and pro-inflammatory cytokines and chemokines in the pancreas and lung. SiRNA treatment attenuated inflammation in the pancreas and lungs of mice following caerulein-induced acute pancreatitis. MPO activity increased in caerulein-induced acute pancreatitis (16.21 +/- 3.571 SD fold increase over control) and treatment with siRNA significantly reduced this (mean 3.555 +/- 2.522 SD fold increase over control) (p < 0.0001). Similarly, lung MPO activity increased following treatment with caerulein (3.56 +/- 0.941 SD fold increase over control) while siRNA treatment significantly reduced MPO activity (0.8243 +/- 0.4353 SD fold increase over control) (p < 0.0001). Caerulein treatment increased plasma amylase activity (7094 +/- 207 U/l) and this significantly decreased following siRNA administration (5895 +/- 115 U/l) (p < 0.0001). Cytokine and chemokine levels in caerulein-induced acute pancreatitis reduced following treatment with siRNA. For example, siRNA treatment significantly decreased pancreatic and lung monocyte chemoattractant protein (MCP)-1 (169.8 +/- 59.75 SD; 90.01 +/- 46.97 SD pg/ml, respectively) compared to caerulein-treated mice (324.7 +/- 103.9 SD; 222.8 +/- 85.37 SD pg/ml, pancreas and lun,g respectively) (p < 0.0001). These findings show a crucial pro-inflammatory role for H2S synthesised by CSE in macrophages in acute pancreatitis and suggest CSE gene silencing with siRNA as a potential therapeutic approach for this condition.
Details
- Title: Subtitle
- Cystathionine-gamma-lyase gene silencing with siRNA in monocytes/macrophages protects mice against acute pancreatitis
- Creators
- A. Badiei - University of OtagoS. T. Chambers - University of OtagoR. R. Gaddam - University of OtagoR. Fraser - University of OtagoM. Bhatia - University of Otago
- Resource Type
- Journal article
- Publication Details
- Applied microbiology and biotechnology, Vol.100(1), pp.337-346
- Publisher
- Springer Nature
- DOI
- 10.1007/s00253-015-6989-z
- PMID
- 26411454
- ISSN
- 0175-7598
- eISSN
- 1432-0614
- Number of pages
- 10
- Grant note
- Infection Research Group (Department of Pathology, University of Otago, Christchurch) 110443.01.Q.PZ / Maurice and Phyllis Paykel Trust
- Language
- English
- Date published
- 01/01/2016
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984446276102771
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