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Metabolic Brain Disease

, Volume 26, Issue 2, pp 107–113 | Cite as

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

  • Sandhya Subramanian
  • Galit Shahaf
  • Eyal Ozeri
  • Lisa M. Miller
  • Arthur A. Vandenbark
  • Eli C. Lewis
  • Halina OffnerEmail author
Original Paper

Abstract

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.

Keywords

hAAT EAE Tregs Pro-inflammatory cytokines CCR6 

Notes

Acknowledgments

The authors wish to thank Ms. Eva Niehaus for assistance with manuscript preparation.

This work was supported by the Biomedical Laboratory R&D Service, Department of Veterans’ Affairs and the Israel Science Foundation 1027/07.

Conflict of interest

None

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Sandhya Subramanian
    • 1
  • Galit Shahaf
    • 2
  • Eyal Ozeri
    • 2
  • Lisa M. Miller
    • 1
    • 3
  • Arthur A. Vandenbark
    • 1
    • 3
    • 4
  • Eli C. Lewis
    • 2
  • Halina Offner
    • 1
    • 3
    • 5
    Email author
  1. 1.Neuroimmunology Research RD-31Portland VA Medical CenterPortlandUSA
  2. 2.Ben-Gurion University of the NegevFaculty of Health SciencesBeer-ShevaIsrael
  3. 3.Department of NeurologyOregon Health & Science UniversityPortlandUSA
  4. 4.Department of Molecular Microbiology & ImmunologyOregon Health & Science UniversityPortlandUSA
  5. 5.Department of Anesthesiology and Perioperative MedicineOregon Health & Science UniversityPortlandUSA

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