Back to Search
Start Over
CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice
- Publication Year :
- 2015
- Publisher :
- American Diabetes Association Inc., 2015.
-
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 β-cells holds the potential to make a significant change in the approach to management of human T1D.
- Subjects :
- Chemokine
mice
Endocrinology, Diabetes and Metabolism
Biology
Pharmacology
Sulfonamide
Receptors, Interleukin-8B
Diabetes Mellitus, Experimental
Receptors, Interleukin-8A
Chemokine receptor
Mice
Mice, Inbred NOD
Journal Article
medicine
Internal Medicine
Animals
CXC chemokine receptors
Receptor
NOD mice
Sulfonamides
Animal
Research Support, Non-U.S. Gov't
Pancreatic islets
Islets of Langerhan
Streptozotocin
medicine.disease
medicine.anatomical_structure
Diabetes Mellitus, Type 1
Immunology
biology.protein
islets of Langerhans
Insulitis
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....cdf352c276fb7b9137aee91e8987c64e