RGD Reference Report - Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis. - Rat Genome Database

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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.
RGD ID: 9999395
Pubmed: PMID:22436018   (View Abstract at PubMed)
PMCID: PMC3352067   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2202-13-30   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Encephalomyelitis treatmentISOSlpi (Rattus norvegicus) and Slpi (Mus musculus)9999395 RGD 
Experimental Autoimmune Encephalomyelitis treatmentIDA 9999395; 9999395 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Slpi  (secretory leukocyte peptidase inhibitor)

Genes (Mus musculus)
Slpi  (secretory leukocyte peptidase inhibitor)

Genes (Homo sapiens)
SLPI  (secretory leukocyte peptidase inhibitor)


Additional Information