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 Vandenbark, Eli C. Lewis, Halina Offner

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalMetabolic Brain Disease
Volume26
Issue number2
DOIs
StatePublished - Jun 2011

Fingerprint

alpha 1-Antitrypsin
Autoimmune Experimental Encephalomyelitis
Regulatory T-Lymphocytes
Autoimmune Diseases
Cells
Inflammation
Caspase 1
Peptides
Serine Proteinase Inhibitors
Interleukin-17
Demyelinating Diseases
Interleukin-1
Surface-Active Agents
Transgenic Mice
Population
Multiple Sclerosis
Interleukin-6
Anti-Inflammatory Agents
Cytokines
Therapeutics

Keywords

  • CCR6
  • EAE
  • hAAT
  • Pro-inflammatory cytokines
  • Tregs

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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. / Subramanian, Sandhya; Shahaf, Galit; Ozeri, Eyal; Miller, Lisa M.; Vandenbark, Arthur; Lewis, Eli C.; Offner, Halina.

In: Metabolic Brain Disease, Vol. 26, No. 2, 06.2011, p. 107-113.

Research output: Contribution to journalArticle

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