CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice.
Diabetes
; 64(4): 1329-40, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25315007
ABSTRACT
Chemokines and their receptors have been associated with or implicated in the pathogenesis of type 1 diabetes (T1D), but the identification of a single specific chemokine/receptor pathway that may constitute a suitable target for the development of therapeutic interventions is still lacking. Here, we used multiple low-dose (MLD) streptozotocin (STZ) injections and the NOD mouse model to investigate the potency of CXCR1/2 inhibition to prevent inflammation- and autoimmunity-mediated damage of pancreatic islets. Reparixin and ladarixin, noncompetitive allosteric inhibitors, were used to pharmacologically blockade CXCR1/2. Transient blockade of said receptors was effective in preventing inflammation-mediated damage in MLD-STZ and in preventing and reversing diabetes in NOD mice. Blockade of CXCR1/2 was associated with inhibition of insulitis and modification of leukocytes distribution in blood, spleen, bone marrow, and lymph nodes. Among leukocytes, CXCR2(+) myeloid cells were the most decreased subpopulations. Together these results identify CXCR1/2 chemokine receptors as "master regulators" of diabetes pathogenesis. The demonstration that this strategy may be successful in preserving residual ß-cells holds the potential to make a significant change in the approach to management of human T1D.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Islotes Pancreáticos
/
Receptores de Interleucina-8A
/
Receptores de Interleucina-8B
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Diabetes Mellitus Experimental
/
Diabetes Mellitus Tipo 1
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia