TY - JOUR
T1 - Sustained expression of circulating human alpha-1 antitrypsin reduces inflammation, increases CD4+FoxP3+ Treg cell population and prevents signs of experimental autoimmune encephalomyelitis in mice
AU - Subramanian, Sandhya
AU - Shahaf, Galit
AU - Ozeri, Eyal
AU - Miller, Lisa M.
AU - Vandenbark, Arthur A.
AU - Lewis, Eli C.
AU - Offner, Halina
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), compared to WT C57BL/6 control mice. According to the results, sustained levels of circulating hAAT profoundly inhibited induction of clinical signs, inflammatory lesions and demyelination observed in WT mice with EAE, concomitant with enhanced levels of CD4+FoxP3+ Treg cells, reduced secretion of MOG peptide-induced pro-inflammatory cytokines, IL-17, IL-1β & IL-6, diminished expression of caspase-1 and enhanced expression of CCR6. These results implicate hAAT as a potent immunoregulatory agent worthy of further investigation as a potential therapy in human autoimmune diseases including multiple sclerosis.
AB - Alpha-1-antitrypsin (AAT) is the primary circulating serine protease inhibitor, and is known to exert potent anti-inflammatory effects and to inhibit the progression of several autoimmune diseases. In this study, transgenic mice that over-express surfactant-driven human (h)AAT on the C57BL/6 background were evaluated for resistance to MOG-35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE), compared to WT C57BL/6 control mice. According to the results, sustained levels of circulating hAAT profoundly inhibited induction of clinical signs, inflammatory lesions and demyelination observed in WT mice with EAE, concomitant with enhanced levels of CD4+FoxP3+ Treg cells, reduced secretion of MOG peptide-induced pro-inflammatory cytokines, IL-17, IL-1β & IL-6, diminished expression of caspase-1 and enhanced expression of CCR6. These results implicate hAAT as a potent immunoregulatory agent worthy of further investigation as a potential therapy in human autoimmune diseases including multiple sclerosis.
KW - CCR6
KW - EAE
KW - Pro-inflammatory cytokines
KW - Tregs
KW - hAAT
UR - http://www.scopus.com/inward/record.url?scp=79959379140&partnerID=8YFLogxK
U2 - 10.1007/s11011-011-9239-9
DO - 10.1007/s11011-011-9239-9
M3 - Article
C2 - 21437674
AN - SCOPUS:79959379140
SN - 0885-7490
VL - 26
SP - 107
EP - 113
JO - Metabolic Brain Disease
JF - Metabolic Brain Disease
IS - 2
ER -