Volume 6, Issue 7(Suppl)
J Gastrointest Dig Syst 2016
ISSN: 2161-069X JGDS, an open access journal
Page 29
Notes:
Gastro Congress 2016
October 24-25, 2016
conferenceseries
.com
October 24-25, 2016 Valencia, Spain
9
th
Euro Global
Gastroenterology Conference
Anti-inflammatory effect of angiotensin 1-7 (Ang 1-7) in the mouse DSS colitis model
Maitham Khajah, Maryam Fateel, Kethireddy Ananthalakshmi
and
Yunus Luqmani
Kuwait University, Kuwait
Background
: The role of angiotensin II (Ang II) in the pathogenesis of inflammatory bowel disease (IBD) is well documented
but little is known of its more recently identified counter-regulatory peptide Ang1-7 and its signaling pathway ACE2/Ang 1-7/
mas
. Enhanced ACE2 expression has been observed in patients with IBD suggesting a role in its pathogenesis.
Aim
: To determine the role of Ang 1-7 in modulating colitis severity
in vivo
using the mouse DSS colitis model, and its effect
on immune cell functions
in vitro
.
Methods
: DSS (3.5% w/v) was used to induce colitis in BALB/C mice and its severity was determined by gross and histological
assessments, daily weight changes, and differential WBC counts. Plasma levels of several cytokines and chemokines was
measured by proteome profiler kit from R&D systems. Colonic protein level for Ang II, ACE2,
mas
receptor, P-ERK1/2,
P-p38MAPK, and P-Akt was determined by western blotting and immunofluorescence. Immune cell chemotaxis, apoptosis,
and superoxide release was determined using the under agarose assay, Annexin-V/7AAD assay, and luminol oxidation kit
respectively.
Results
: Enhanced AngII, ACE2, and MasR1 expression was observed in the colon of mice after DSS treatment. Daily IP
injections with Ang 1-7 (0.01-0.06 mg/kg, at both prophylactic and treatment approaches) significantly reduced colitis severity
at gross and histological level, reduced phosphorylated levels of ERK1/2, p38, and Akt in the colon, and significantly reduced
plasma levels of various cytokines and chemokines. Also, Ang 1-7 treatment significantly reduced neutrophil chemotaxis and
superoxide release in response to WKYMVm (fMLP-peptide) stimulation, and increased neutrophil and mononuclear cell
spontaneous apoptosis.
Conclusion
: Ang 1-7 is a promising future therapeutic approach to control colitis severity in part through modulating the
activity of various inflammatory signaling molecules, levels of various cytokines and chemokines, and immune cell functions
which all are important for the inflammatory process.
Biography
Maitham Khajah has completed his BPharm degree from Faculty of Pharmacy, Kuwait University and obtained his PhD degree from the University of Calgary,
Canada. He is currently an Assistant Professor in Kuwait University, Faculty of Pharmacy- Department of Pharmacology & Therapeutics since January 2010. His
research interest focuses on studying new targets for the treatment of inflammatory bowel disease. He published various abstracts and peer reviewed manuscripts
in international journals. He co-supervised many students for the MSc Molecular Biology Program. Since, he joined Kuwait University, he got various grants as PI
and Co-I. He was awarded the Best Young Researcher Award by Kuwait University for the year 2013 – 2014.
maitham@HSC.EDU.KWMaitham Khajah et al., J Gastrointest Dig Syst 2016, 6:7(Suppl)
http://dx.doi.org/10.4172/2161-069X.C1.043