RGD Reference Report - Low-dose warfarin functions as an immunomodulator to prevent cyclophosphamide-induced NOD diabetes. - Rat Genome Database

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Low-dose warfarin functions as an immunomodulator to prevent cyclophosphamide-induced NOD diabetes.

Authors: Kurohara, M  Yasuda, H  Moriyama, H  Nakayama, M  Sakata, M  Yamada, K  Kotani, R  Hara, K  Yokono, K  Nagata, M 
Citation: Kurohara M, etal., Kobe J Med Sci. 2008 May 23;54(1):E1-13.
RGD ID: 2307287
Pubmed: PMID:18772604   (View Abstract at PubMed)

Warfarin has been used as an anticoagulant for a long time. Recently, the pleiotropic effect of warfarin has been investigated. As low-dose warfarin has been reported to have anti-inflammatory effect through suppression of IL-6 secretion and inhibit the immune-associated signal between Tyro3 and its ligand, Gas6, the effect of low-dose warfarin on autoimmune diabetes in NOD mice was examined. To investigate the anti-inflammatory effect of warfarin, IL-6 secretion by splenocytes was examined in the presence of various concentrations of warfarin. Low concentration of warfarin inhibited IL-6 secretion. mRNA expression of Rse, one of the Tyro3 receptor family members, and Gas6 were analyzed in NOD mice. It was detected in islets, splenocytes and bone-marrow derived dendritic cells. 0.25 mg/l or 0.50 mg/l of warfarin was orally administered to NOD mice as a cyclophosphamide-induced diabetes model. Oral administration of warfarin at much lower doses than those clinically used as an anticoagulant significantly reduced the degree of insulitis and diabetes incidence in this model. We previously demonstrated that anti-FasL Ab-treatment led to complete prevention of autoimmune diabetes in NOD mice. As Fas/FasL signaling is reported to be essential for cyclophosphamide-induced diabetes model, we extracted RNA from lymphocytes of the inguinal lymph nodes of anti-FasL Ab-treated NOD mice and performed real-time PCR to determine expression of Rse gene. Interestingly, the expression of Rse gene related to the blockade of Fas/FasL signaling was reduced to less than half the level of untreated mice. In conclusion, low-dose warfarin is a potential immunomodulator which can prevent autoimmune diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pancreas disease  ISOIl6 (Mus musculus)2307287; 2307287insulitis associated with Diabetes Mellitus more ...RGD 
pancreas disease  IAGP 2307287insulitis associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)

Genes (Mus musculus)
Il6  (interleukin 6)

Genes (Homo sapiens)
IL6  (interleukin 6)


Additional Information