Purchase this article with an account.
V. L. Calder, G. Galatowicz, L. Joshi, R. C. Howes, P. Adamson; Anti-Inflammatory Role for Sirtuin-1 Activators in a Peptide-Induced B10riii Model of Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):829.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Sirtuins are protein deacetylases involved in signal transduction which are thought to possess neuroprotective and anti-inflammatory properties. The aim of this study is to determine the effect of sirtuin-1 (SIRT-1) activators in an IRBP peptide-induced model of experimental autoimmune uveitis (EAU).
Female B10RIII.7ins mice (6-8 weeks) were subcutaneously immunized with peptide 161-180 [300pg] emulsified in mycobacterium-supplemented complete Freunds’ adjuvant, and pertussis given intraperitoneally. Mice were treated once daily by oral gavage with SRT-2379 [100mg/kg/day] or vehicle control from day 0-7, or received no treatment. Eyes were processed at day 14 for histology, and superficial cervical lymph nodes (PLN) harvested for assaying T cell proliferation to immunizing peptide, cytokine production by multiplex bead arrays and intracellular cytokine expression for flow cytometry.
The clinical scores were significantly decreased in the SRT-2379-treated EAU mice in comparison with the vehicle gavage treated EAU mice (P=0.011). The mean histological score in SRT-2379-treated EAU mice (n=5) was 1.11+/-0.5, which was significantly decreased in comparison with vehicle-treated EAU mice (n=6; 2.73+/-0.62; P<0.02) and with untreated EAU mice (3.66+/-0.84; P<0.02). PLN cells proliferated to peptide in all EAU groups and PLN cell production of TNF-alpha was detected in all EAU groups at 24-72hr post stimulation in the presence or absence of exogenously added peptide. In contrast, interferon-gamma and interleukin-17 were only produced in response to peptide, maximally at 48-72 hr. IL-4 was not detected.
SIRT-1 activators were anti-inflammatory in this model of EAU.
This PDF is available to Subscribers Only