Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis.

Authors: Muller, AM  Jun, E  Conlon, H  Sadiq, SA 
Citation: Muller AM, etal., BMC Neurosci. 2012 Mar 21;13:30. doi: 10.1186/1471-2202-13-30.
Pubmed: (View Article at PubMed) PMID:22436018
DOI: Full-text: DOI:10.1186/1471-2202-13-30

BACKGROUND: The secretory leukocyte protease inhibitor (SLPI) exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown METHODS: To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-beta. RESULTS: The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-beta and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. In vitro, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25(hi) CD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-beta to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation. CONCLUSION: In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.

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CRRD ID: 9999395
Created: 2015-04-16
Species: All species
Last Modified: 2015-04-16
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.