AMP-activated protein kinase (AMPK) is an energy sensing metabolic switch in mammalian cells. Here, we report our novel finding that AMPK is lost in all immune cells of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of Central Nervous System (CNS). AMPKα1 is predominantly expressed in T cells and antigen presenting cells (APCs), which are primarily involved in EAE disease progression. AMPK is lost at protein level in spleen macrophages, total T cells and their subsets (CD4, CD8 and regulatory T cells) isolated from EAE afflicted animals compared to control, without affecting its mRNA levels suggesting that the loss of AMPK protein is the result of posttranscriptional modification. To examine its pathological relevance in inflammatory disease, EAE was induced in wild type (+/+) and AMPKα1 null mice (-/-) using MOG35-55 peptide. AMPKα1-/- mice exhibited severe EAE disease with profound infiltration of mononuclear cells compared to wild type mice however, AMPKα2 is not involved in enhancing the severity of the disease. Spleen cells isolated from AMPKα1-/- immunized mice exhibited a significant induction in the production of IFNγ. Our study identifies AMPK as a down regulated target during disease in all immune cells and possibly restoring AMPK may serve as a novel therapeutic target in autoimmune diseases like multiple sclerosis (MS).
|Original language||English (US)|
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Aug 14 2009|
Bibliographical noteFunding Information:
The authors thank Ms. Joyce Bryan and Carrie Barnes for their technical assistance. Authors also acknowledge generous support of Prof. Inderjit Singh for providing infrastructure for conducting this study. This investigation (S.G.) was supported by Grants (RG 3810-A-1, PP1283) from the National Multiple Sclerosis Society. This work was also supported by Extramural Research Facilities Program of the National Center for Research Resources (Grants C06 RR018823 and No C06 RR015455). C.d.M. is supported by the Fund for Scientific Research in Industry and Agriculture (F.R.I.A.), Belgium. L.B. is Research Associate of the Fonds National de la Recherche Scientifique, Belgium.
- Multiple sclerosis
- T cells